<?xml version="1.0" encoding="us-ascii"?>
<!-- RRD ActiveDisclosure(SM) XBRL Linkbase Document - http://www.financial.rrd.com/ -->
<!-- Creation Date      : 2016-08-03T02:02:44.0105549+00:00 -->
<!-- Version            : 2.3.4.12 -->
<!-- Package ID         : C22956020815B1D1C92FB92292DCE92E-0001582313-001605 -->
<!-- Copyright (c) 2016 R. R. Donnelley & Sons Company. All Rights Reserved. -->
<linkbase xmlns="http://www.xbrl.org/2003/linkbase" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <arcroleRef xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all" arcroleURI="http://xbrl.org/int/dim/arcrole/all" />
  <arcroleRef xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default" arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" />
  <arcroleRef xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain" arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" />
  <arcroleRef xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member" arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" />
  <arcroleRef xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension" arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" />
  <roleRef xlink:type="simple" xlink:href="xene-20160630.xsd#TemplateLink" roleURI="http://www.xenon-pharma.com/20160630/role/TemplateLink" />
  <roleRef roleURI="http://www.xenon-pharma.com/20160630/taxonomy/role/StatementStatementOfShareholdersEquityUnaudited" xlink:href="xene-20160630.xsd#Role_StatementStatementOfShareholdersEquityUnaudited" xlink:type="simple" />
  <definitionLink xlink:type="extended" xlink:role="http://www.xenon-pharma.com/20160630/taxonomy/role/StatementStatementOfShareholdersEquityUnaudited">
    <loc xlink:href="xene-20160630.xsd#xene_AdjustmentsToAdditionalPaidInCapitalFairValueAdjustmentUponReclassificationOfStockOptions" xlink:type="locator" xlink:label="xene_AdjustmentsToAdditionalPaidInCapitalFairValueAdjustmentUponReclassificationOfStockOptions" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised" xlink:type="locator" xlink:label="us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised" xlink:type="locator" xlink:label="us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalShareBasedCompensationStockOptionsRequisiteServicePeriodRecognition" xlink:type="locator" xlink:label="us-gaap_AdjustmentsToAdditionalPaidInCapitalShareBasedCompensationStockOptionsRequisiteServicePeriodRecognition" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_NetIncomeLoss" xlink:type="locator" xlink:label="us-gaap_NetIncomeLoss" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_SharesOutstanding" xlink:type="locator" xlink:label="us-gaap_SharesOutstanding" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_StockholdersEquity" xlink:type="locator" xlink:label="us-gaap_StockholdersEquity" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember" xlink:type="locator" xlink:label="us-gaap_AccumulatedOtherComprehensiveIncomeMember" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_RetainedEarningsMember" xlink:type="locator" xlink:label="us-gaap_RetainedEarningsMember" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AdditionalPaidInCapitalMember" xlink:type="locator" xlink:label="us-gaap_AdditionalPaidInCapitalMember" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_CommonStockMember" xlink:type="locator" xlink:label="us-gaap_CommonStockMember" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_EquityComponentDomain" xlink:type="locator" xlink:label="us-gaap_EquityComponentDomain_2" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_EquityComponentDomain" xlink:type="locator" xlink:label="us-gaap_EquityComponentDomain" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_StatementEquityComponentsAxis" xlink:type="locator" xlink:label="us-gaap_StatementEquityComponentsAxis" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_StatementTable" xlink:type="locator" xlink:label="us-gaap_StatementTable" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_StatementLineItems" xlink:type="locator" xlink:label="us-gaap_StatementLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_StatementEquityComponentsAxis" order="10040.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_StatementEquityComponentsAxis" xlink:to="us-gaap_EquityComponentDomain_2" order="10060.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_StatementEquityComponentsAxis" xlink:to="us-gaap_EquityComponentDomain" order="10060.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_EquityComponentDomain" xlink:to="us-gaap_CommonStockMember" order="10080.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_EquityComponentDomain" xlink:to="us-gaap_AdditionalPaidInCapitalMember" order="10120.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_EquityComponentDomain" xlink:to="us-gaap_RetainedEarningsMember" order="10140.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_EquityComponentDomain" xlink:to="us-gaap_AccumulatedOtherComprehensiveIncomeMember" order="10160.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StockholdersEquity" order="10190.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_SharesOutstanding" order="10430.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_NetIncomeLoss" order="10590.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_AdjustmentsToAdditionalPaidInCapitalShareBasedCompensationStockOptionsRequisiteServicePeriodRecognition" order="10770.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised" order="10950.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised" order="11170.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_StatementLineItems" xlink:to="xene_AdjustmentsToAdditionalPaidInCapitalFairValueAdjustmentUponReclassificationOfStockOptions" order="11330.00" priority="2" use="optional" />
  </definitionLink>
  <roleRef roleURI="http://www.xenon-pharma.com/20160630/taxonomy/role/DisclosureCollaborationAgreementsRevenueRecognizedFromCollaborationsDetails" xlink:href="xene-20160630.xsd#Role_DisclosureCollaborationAgreementsRevenueRecognizedFromCollaborationsDetails" xlink:type="simple" />
  <definitionLink xlink:type="extended" xlink:role="http://www.xenon-pharma.com/20160630/taxonomy/role/DisclosureCollaborationAgreementsRevenueRecognizedFromCollaborationsDetails">
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_LicenseAndServicesRevenue" xlink:type="locator" xlink:label="us-gaap_LicenseAndServicesRevenue" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_CollaborativeArrangementMember" xlink:type="locator" xlink:label="us-gaap_CollaborativeArrangementMember" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:type="locator" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember_2" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:type="locator" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:type="locator" xlink:label="us-gaap_TypeOfArrangementAxis" />
    <loc xlink:href="xene-20160630.xsd#xene_ResearchFundingMember" xlink:type="locator" xlink:label="xene_ResearchFundingMember" />
    <loc xlink:href="xene-20160630.xsd#xene_RecognitionOfUpfrontPaymentMember" xlink:type="locator" xlink:label="xene_RecognitionOfUpfrontPaymentMember" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" xlink:type="locator" xlink:label="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_2" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" xlink:type="locator" xlink:label="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis" xlink:type="locator" xlink:label="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis" />
    <loc xlink:href="xene-20160630.xsd#xene_GenentechMember" xlink:type="locator" xlink:label="xene_GenentechMember" />
    <loc xlink:href="xene-20160630.xsd#xene_TevaPharmaceuticalIndustriesLtdMember" xlink:type="locator" xlink:label="xene_TevaPharmaceuticalIndustriesLtdMember" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_RepurchaseAgreementCounterpartyNameDomain" xlink:type="locator" xlink:label="us-gaap_RepurchaseAgreementCounterpartyNameDomain_2" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_RepurchaseAgreementCounterpartyNameDomain" xlink:type="locator" xlink:label="us-gaap_RepurchaseAgreementCounterpartyNameDomain" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_CounterpartyNameAxis" xlink:type="locator" xlink:label="us-gaap_CounterpartyNameAxis" />
    <loc xlink:href="xene-20160630.xsd#xene_CollaborationRevenueArrangementByTypeTable" xlink:type="locator" xlink:label="xene_CollaborationRevenueArrangementByTypeTable" />
    <loc xlink:href="xene-20160630.xsd#xene_CollaborationRevenueLineItems" xlink:type="locator" xlink:label="xene_CollaborationRevenueLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="xene_CollaborationRevenueLineItems" xlink:to="xene_CollaborationRevenueArrangementByTypeTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="xene_CollaborationRevenueArrangementByTypeTable" xlink:to="us-gaap_CounterpartyNameAxis" order="10040.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_CounterpartyNameAxis" xlink:to="us-gaap_RepurchaseAgreementCounterpartyNameDomain_2" order="10060.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_CounterpartyNameAxis" xlink:to="us-gaap_RepurchaseAgreementCounterpartyNameDomain" order="10060.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_RepurchaseAgreementCounterpartyNameDomain" xlink:to="xene_TevaPharmaceuticalIndustriesLtdMember" order="10080.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_RepurchaseAgreementCounterpartyNameDomain" xlink:to="xene_GenentechMember" order="10140.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="xene_CollaborationRevenueArrangementByTypeTable" xlink:to="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis" order="10170.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis" xlink:to="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_2" order="10190.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis" xlink:to="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" order="10190.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" xlink:to="xene_RecognitionOfUpfrontPaymentMember" order="10210.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain" xlink:to="xene_ResearchFundingMember" order="10230.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="xene_CollaborationRevenueArrangementByTypeTable" xlink:to="us-gaap_TypeOfArrangementAxis" order="10280.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember_2" order="10300.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_TypeOfArrangementAxis" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember" order="10300.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:to="us-gaap_CollaborativeArrangementMember" order="10320.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="xene_CollaborationRevenueLineItems" xlink:to="us-gaap_LicenseAndServicesRevenue" order="10410.00" priority="2" use="optional" />
  </definitionLink>
  <roleRef roleURI="http://www.xenon-pharma.com/20160630/taxonomy/role/DisclosureCommitmentsAndContingenciesDetails" xlink:href="xene-20160630.xsd#Role_DisclosureCommitmentsAndContingenciesDetails" xlink:type="simple" />
  <definitionLink xlink:type="extended" xlink:role="http://www.xenon-pharma.com/20160630/taxonomy/role/DisclosureCommitmentsAndContingenciesDetails">
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_PrepaidExpenseNoncurrent" xlink:type="locator" xlink:label="us-gaap_PrepaidExpenseNoncurrent" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_PrepaidExpenseCurrent" xlink:type="locator" xlink:label="us-gaap_PrepaidExpenseCurrent" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_CostOfServices" xlink:type="locator" xlink:label="us-gaap_CostOfServices" />
    <loc xlink:href="xene-20160630.xsd#xene_ContractualObligationPaid" xlink:type="locator" xlink:label="xene_ContractualObligationPaid" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ContractualObligation" xlink:type="locator" xlink:label="us-gaap_ContractualObligation" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_UnrecordedUnconditionalPurchaseObligationTerm" xlink:type="locator" xlink:label="us-gaap_UnrecordedUnconditionalPurchaseObligationTerm" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementMember" xlink:type="locator" xlink:label="us-gaap_ResearchAndDevelopmentArrangementMember" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_LongTermPurchaseCommitmentCategoryOfItemPurchasedDomain" xlink:type="locator" xlink:label="us-gaap_LongTermPurchaseCommitmentCategoryOfItemPurchasedDomain_2" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_LongTermPurchaseCommitmentCategoryOfItemPurchasedDomain" xlink:type="locator" xlink:label="us-gaap_LongTermPurchaseCommitmentCategoryOfItemPurchasedDomain" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_LongTermPurchaseCommitmentByCategoryOfItemPurchasedAxis" xlink:type="locator" xlink:label="us-gaap_LongTermPurchaseCommitmentByCategoryOfItemPurchasedAxis" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_UnrecordedUnconditionalPurchaseObligationTable" xlink:type="locator" xlink:label="us-gaap_UnrecordedUnconditionalPurchaseObligationTable" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_UnrecordedUnconditionalPurchaseObligationLineItems" xlink:type="locator" xlink:label="us-gaap_UnrecordedUnconditionalPurchaseObligationLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_UnrecordedUnconditionalPurchaseObligationLineItems" xlink:to="us-gaap_UnrecordedUnconditionalPurchaseObligationTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_UnrecordedUnconditionalPurchaseObligationTable" xlink:to="us-gaap_LongTermPurchaseCommitmentByCategoryOfItemPurchasedAxis" order="10040.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_LongTermPurchaseCommitmentByCategoryOfItemPurchasedAxis" xlink:to="us-gaap_LongTermPurchaseCommitmentCategoryOfItemPurchasedDomain_2" order="10060.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_LongTermPurchaseCommitmentByCategoryOfItemPurchasedAxis" xlink:to="us-gaap_LongTermPurchaseCommitmentCategoryOfItemPurchasedDomain" order="10060.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LongTermPurchaseCommitmentCategoryOfItemPurchasedDomain" xlink:to="us-gaap_ResearchAndDevelopmentArrangementMember" order="10080.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_UnrecordedUnconditionalPurchaseObligationLineItems" xlink:to="us-gaap_UnrecordedUnconditionalPurchaseObligationTerm" order="10210.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_UnrecordedUnconditionalPurchaseObligationLineItems" xlink:to="us-gaap_ContractualObligation" order="10310.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_UnrecordedUnconditionalPurchaseObligationLineItems" xlink:to="xene_ContractualObligationPaid" order="10410.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_UnrecordedUnconditionalPurchaseObligationLineItems" xlink:to="us-gaap_CostOfServices" order="10510.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_UnrecordedUnconditionalPurchaseObligationLineItems" xlink:to="us-gaap_PrepaidExpenseCurrent" order="10610.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_UnrecordedUnconditionalPurchaseObligationLineItems" xlink:to="us-gaap_PrepaidExpenseNoncurrent" order="10730.00" priority="2" use="optional" />
  </definitionLink>
  <roleRef roleURI="http://www.xenon-pharma.com/20160630/taxonomy/role/DisclosureRelatedPartiesDetails" xlink:href="xene-20160630.xsd#Role_DisclosureRelatedPartiesDetails" xlink:type="simple" />
  <definitionLink xlink:type="extended" xlink:role="http://www.xenon-pharma.com/20160630/taxonomy/role/DisclosureRelatedPartiesDetails">
    <loc xlink:href="xene-20160630.xsd#xene_PrepaidExpenseCurrentAndNonCurrentRelatedParty" xlink:type="locator" xlink:label="xene_PrepaidExpenseCurrentAndNonCurrentRelatedParty" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_CostsAndExpensesRelatedParty" xlink:type="locator" xlink:label="us-gaap_CostsAndExpensesRelatedParty" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_MinorityInterestOwnershipPercentageByNoncontrollingOwners" xlink:type="locator" xlink:label="us-gaap_MinorityInterestOwnershipPercentageByNoncontrollingOwners" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_MinimumMember" xlink:type="locator" xlink:label="us-gaap_MinimumMember" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_RangeMember" xlink:type="locator" xlink:label="us-gaap_RangeMember_2" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_RangeMember" xlink:type="locator" xlink:label="us-gaap_RangeMember" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_RangeAxis" xlink:type="locator" xlink:label="us-gaap_RangeAxis" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BeneficialOwnerMember" xlink:type="locator" xlink:label="us-gaap_BeneficialOwnerMember" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_RelatedPartyDomain" xlink:type="locator" xlink:label="us-gaap_RelatedPartyDomain_2" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_RelatedPartyDomain" xlink:type="locator" xlink:label="us-gaap_RelatedPartyDomain" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" xlink:type="locator" xlink:label="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementMember" xlink:type="locator" xlink:label="us-gaap_ResearchAndDevelopmentArrangementMember" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_LongTermPurchaseCommitmentCategoryOfItemPurchasedDomain" xlink:type="locator" xlink:label="us-gaap_LongTermPurchaseCommitmentCategoryOfItemPurchasedDomain" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_LongTermPurchaseCommitmentByCategoryOfItemPurchasedAxis" xlink:type="locator" xlink:label="us-gaap_LongTermPurchaseCommitmentByCategoryOfItemPurchasedAxis" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable" xlink:type="locator" xlink:label="us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable" />
    <loc xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_RelatedPartyTransactionLineItems" xlink:type="locator" xlink:label="us-gaap_RelatedPartyTransactionLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="us-gaap_RelatedPartyTransactionLineItems" xlink:to="us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable" order="10010.00" priority="2" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable" xlink:to="us-gaap_LongTermPurchaseCommitmentByCategoryOfItemPurchasedAxis" order="10040.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_LongTermPurchaseCommitmentByCategoryOfItemPurchasedAxis" xlink:to="us-gaap_LongTermPurchaseCommitmentCategoryOfItemPurchasedDomain" order="10060.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_LongTermPurchaseCommitmentCategoryOfItemPurchasedDomain" xlink:to="us-gaap_ResearchAndDevelopmentArrangementMember" order="10080.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable" xlink:to="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" order="10130.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" xlink:to="us-gaap_RelatedPartyDomain_2" order="10150.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" xlink:to="us-gaap_RelatedPartyDomain" order="10150.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_RelatedPartyDomain" xlink:to="us-gaap_BeneficialOwnerMember" order="10170.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable" xlink:to="us-gaap_RangeAxis" order="10180.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="us-gaap_RangeAxis" xlink:to="us-gaap_RangeMember_2" order="10200.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="us-gaap_RangeAxis" xlink:to="us-gaap_RangeMember" order="10200.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_RangeMember" xlink:to="us-gaap_MinimumMember" order="10220.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_RelatedPartyTransactionLineItems" xlink:to="us-gaap_MinorityInterestOwnershipPercentageByNoncontrollingOwners" order="10250.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_RelatedPartyTransactionLineItems" xlink:to="us-gaap_CostsAndExpensesRelatedParty" order="10370.00" priority="2" use="optional" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="us-gaap_RelatedPartyTransactionLineItems" xlink:to="xene_PrepaidExpenseCurrentAndNonCurrentRelatedParty" order="10550.00" priority="2" use="optional" />
  </definitionLink>
</linkbase>
