Hypoxic tumor microenvironment is the bottleneck of the conventional photodynamic therapy (PDT) and significantly weakens the overall therapeutic efficiency. Herein, versatile metal-organic framework (MOF) nanosheets (DBBC-UiO) comprised of bacteriochlorin ligand and Hf6(µ3-O)4(µ3-OH)4 clusters to address this tricky issue are designed. The resulting DBBC-UiO enables numerous superoxide anion radical (O2 -•) generation via a type I mechanism with a 750 nm NIR-laser irradiation, part of which transforms to high toxic hydroxyl radical (OH•) and oxygen (O2) through superoxide dismutase (SOD)-mediated catalytic reactions under severe hypoxic microenvironment (2% O2), and the partial recycled O2 enhances O2 -• generation. Owing to the synergistic radicals, it realizes advanced antitumor performance with 91% cell mortality against cancer cells in vitro, and highly efficient hypoxic solid tumor ablation in vivo. It also accomplishes photoacoustic imaging (PAI) for cancer diagnosis. This DBBC-UiO, taking advantage of superb penetration depth of the 750 nm laser and distinct antihypoxia activities, offers new opportunities for PDT against clinically hypoxic cancer.