Organic　prodrugs　have　been　widely　reported　to　avoid　side　effects　and　have　been　applied　for　precise　tumor　therapy　in　recent　years.　However,　inorganic　nano-prodrugs　with　localized　generation　of　toxic　products　in　the　tumor　have　not　been　reported.　Herein,　we　report　an　inorganic　nano-prodrug,　tellurium　nanowires　(TeNWs),　that　generate　toxic　TeO66-　triggered　by　hydrogen　peroxide　(H2O2)　for　highly　selective　cancer　chemotherapy.　Bovine　serum　albumin　and　dextran　conjugate　coated　TeNWs,　with　a　length　of　∼82　nm　and　a　width　of　∼7　nm,　showed　high　stability　in　physiological　medium.　The　interaction　between　TeNWs　and　intracellular　H2O2　produces　toxic　TeO66-　molecules　greatly　enhanced　ROS　generation,　and　the　reaction　product,　verified　as　TeO66-,　would　react　with　glutathione　(GSH)　and　thus　decrease　intracellular　GSH　levels,　which　greatly　increases　ROS　levels　in　the　tumor.　Importantly,　TeNWs　selectively　kill　cancer　cells　by　caspase-independent　autophagic　death　and　apoptosis,　as　well　as　exerting　an　immune　response,　while　not　affecting　normal　cells　due　to　the　high　H2O2　levels　in　cancer　cells.　Moreover,　after　the　sequential　reaction　with　H2O2　and　GSH,　TeNWs　were　dissociated　into　small　molecules　and　could　be　rapidly　and　completely　removed　from　the　body.　Both　in　vitro　and　in　vivo　experiments　indicate　that　TeNWs　are　a　promising　inorganic　nano-prodrug　that　exerts　good　selective　therapeutic　effects　on　tumors.　©　2019　The　Royal　Society　of　Chemistry.