Biomineralization of enzymes for diagnosis and treatment of diseases remain a considerable challenge, due to their severe reaction conditions and complicated physiological environment. Herein, we reported a biomimetic enzyme cascade delivery nanosystem, tumor-targeted erythrocyte membrane (EM)-cloaked iron-mineralized glucose oxidases (GOx-Fe@EM-A) for enhancing anticancer efficacy by self-activated cascade to generate sufficient high toxic •OH at tumor site. : An ultra-small Fe nanoparticle (FeNP) was anchored in the inner cavity of glucose oxidase (GOx) to form iron-mineralized glucose oxidase (GOx-Fe) as a potential tumor therapeutic nanocatalyst. Moreover, erythrocyte membrane cloaking delivery of GOx-Fe was designed to effectively accumulate ultra-small GOx-Fe at tumor site. : GOx-Fe@EM-A had satisfactory biocompatibility and light-trigged release efficiency. Erythrocyte membrane cloaking of GOx-Fe@EM-A not only prolongs blood circulation but also protects enzyme activity of GOx-Fe; Tumor targeting of GOx-Fe@EM-A endowed preferential accumulation at tumor site. After NIR light irradiation at tumor site, erythrocyte membrane of GOx-Fe@EM-A was ruptured to achieve light-driven release and tumor deep penetration of ultra-small nanosize GOx-Fe by the photothermal effect of ICG. Then, GOx-Fe occurred self-activated cascade to effectively eradicate tumor by producing the highly cumulative and deeply penetrating •OH at tumor site. : Tumor-targeted erythrocyte membrane-cloaked iron-mineralized glucose oxidase (GOx-Fe0@EM-A) exhibits a promising strategy for striking antitumor efficacy by light-driven tumor deep penetration and self-activated therapeutic cascade.