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• Platinum nanoenzyme was anchored on BP NSs to ameliorate tumor hypoxia. • Ce6 was covalently linked to BP/Pt NSs to provide enhanced ROS production in the tumor. • Oxygen self-supplied photodynamic and photothermal synergistic therapy was performed towards 4T1 tumor ablation. Tumor hypoxia can cause undesirable barriers for many therapeutic interventions, especially for oxygen-dependent photodynamic therapy (PDT). To ameliorate hypoxia and enhance the cancer therapeutic efficacy, herein, catalase-like platinum (Pt) nanoparticles (NPs) were designed as nanoenzyme to anchor onto the surface of black phosphorus nanosheets (BP NSs), followed by Ce6 conjugation and subsequent PEGylation to obtain BP/Pt-Ce6@PEG NSs. As-prepared BP/Pt-Ce6@PEG NSs could decompose endogenous H 2 O 2 into O 2 in situ to relieve tumor hypoxia, affording enhanced reactive oxygen species (ROS) production. In vitro cytotoxicity studies demonstrated the best therapeutic effect of BP/Pt-Ce6@PEG NSs in comparison to that of BP/Pt NSs or Ce6 alone. In vivo experiments on the 4T1 tumor xenograft mouse model showed that BP/Pt-Ce6@PEG NSs could efficiently alleviate tumor hypoxia and eliminate tumor cells, presenting excellent oxygen self-supplied photodynamic and photothermal synergistic therapy therapeutic efficacy. These results highlight that platinum nanoenzyme functionalization is promising to raise the intratumoral oxygen level to surmount tumor hypoxia for efficient tumor treatment. [ABSTRACT FROM AUTHOR]