Abstract: A Mn-clusters-porphyrin metal-organic framework nanosheet(nMn-MOF)was synthesized by coordination chelation to enhance photodynamic therapy. The nanosheet was characterized by dynamic light scattering, transmission electron microscopy and X-ray photoelectron spectroscopy. Oxygen sensor and ICG were used to investigate the production of oxygen and the singlet oxygen(¹O₂)generation. The cytotoxicity of the nanosheet against tumor cells were detected by CCK-8 assay, and the anti-hypoxia and oxygen-generation ability of nanosheets were investigated by fluorescence staining assay. The results indicated that this nanosheet could catalyze the intracellular H₂O₂ into O₂, which overcame the tumor hypoxia. Furthermore, the generated oxygen was converted to cytotoxic ¹O₂ under the near infrared light irradiation, thereby enhancing photodynamic therapy.