Conventional oxygen-dependent photodynamic therapy (PDT) has faced severe challenges because of the non-specificity of most available photosensitizers (PSs) and the hypoxic nature of tumor tissues. Here, an O-2 selfsufficient cell-like biomimetic nanoplatform (CAT-PS-ZIF@Mem) consisting of the cancer cell membrane (Mem) and a cytoskeleton-like porous zeolitic imidazolate framework (ZIF-8) with the embedded catalase (CAT) protein molecules and Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4, defined as PS) is developed. Because of the immunological response and homologous targeting abilities of the cancer cell membrane, CAT-PS-ZIF@ Mem is selectively accumulated at the tumor site and taken up effectively by tumor cells after intravenous injection. After the intracellular H2O2 penetration into the framework, it is catalyzed by CAT to produce O-2 at the hypoxic tumor site, facilitating the generation of toxic O-1(2) for highly effective PDT in vivo under near-infrared irradiation. By integrating the immune escape, cell homologous recognition, and O-2 self-sufficiency, this cell-like biomimetic nanoplatform demonstrates highly specific and efficient PDT against hypoxic tumor cells with much reduced side-effect on normal tissues.