Shutting down glucose supply by glucose oxidase (GOx) to starve tumors has been considered to be an attractive strategy in cancerous starvation therapy. Nevertheless, the in vivo applications of GOx-based starvation therapy are severely restricted by the poor GOx delivery efficiency and the self-limiting therapeutic effect. Herein, a biomimetic nanoreactor has been fabricated for starvation-activated cancer therapy by encapsulating GOx and prodrug tirapazamine (TPZ) in an erythrocyte membrane cloaked metal–organic framework (MOF) nanoparticle (TGZ@eM). The fabricated TGZ@eM nanoreactor can assist the delivery of GOx to tumor cells and then exhaust endogenous glucose and O2 to starve tumors efficiently. Importantly, the resulting tumor hypoxia by GOx-based starvation therapy further initiates the activation of TPZ, which is released from the nanoreactor in the acid lyso/endosome environment, for enhanced colon cancer therapy. More importantly, by integrating the biomimetic surface modification, the immunity-escaping and prolonged blood circulation characteristics endow our nanoreactor dramatically improved cancer targeting ability. The in vitro and in vivo outcomes indicate our biomimetic nanoreactor exhibits a strong synergistic cascade effect for colon cancer therapy in an accurate and facile manner.