Copper　nanowires　have　received　extensive　attention　for　their　potential　applications　in　optics,　electricity　and　catalysis,　while　oxidation　erosion　has　become　the　biggest　obstacle　to　their　widespread　application.　Here,　we　present　a　chemo-mechanical　coupling　model　to　investigate　the　interlayer　cracking　behaviors　of　nanowires　during　oxidation.　In　contrast　to　existing　chemomechanical　models,　the　present　model　emphasizes　that　the　process　of　oxygen　entry　into　copper　nanowires　is　chemical　reaction-mediated　layer-by-layer　replacement　rather　than　vacancymediated　diffusion,　which　means　the　oxygen　ions　in　the　outer　layer　would　not　cross　over　the　oxygen　atoms　in　the　inner　layer　during　their　entry.　These　conclusions　are　validated　by　molecular　dynamics　simulations.　We　then　discuss　the　effect　of　the　chemical　reaction-induced　free　energy　on　the　stress　state　of　the　nanowire　during　the　reaction.　Finally,　a　self-developed　finite　difference　procedure　is　used　to　solve　the　control　equations　and　the　fracture　location　is　determined　according　to　the　energy　release　rate　analysis.　We　find　the　fracture　of　nanowires　is　closely　dependent　on　the　size　of　nanowire,　the　reaction　rate　and　the　oxygen　concentration.　This　work　deepens　our　understanding　of　the　mechanism　of　chemo-mechanical　coupling　and　fracture　behavior　of　metals　due　to　oxidation,　thus　has　implications　in　other　areas　involving　chemo-mechanical　coupling.