Local hypoxia in tumors results in undesirable impediments for the efficiencies of oxygen‐dependent chemical and photodynamic therapy (PDT). Herein, a versatile oxygen‐generating and pH‐responsive nanoplatform is developed by loading MnO2 nanodots onto the nanosystem that encapsulates g‐C3N4 and doxorubicin hydrochloride to overcome the hypoxia‐caused resistance in cancer therapy. The loaded MnO2 nanodots can react with endogenous acidic H2O2 to elevate the dissolved oxygen concentration, leading to considerably enhanced cancer therapy efficacy. As such, the as‐prepared nanoplatform with excellent dispersibility and satisfactory biocompatibility can sustainably increase the oxygen concentration and rapidly release the encapsulated drugs in acid H2O2 environment. In vitro cytotoxicity experiments show a higher therapy effect by the designed nanoplatform, when compared to therapy without MnO2 nanodots under hypoxia condition, or chemical and photodynamic therapy alone with the presence of MnO2 nanodots. In vivo experiments also demonstrate that 4T1 tumors can be very efficiently eliminated by the designed nanoplatform under light irradiation. These results highlight that the MnO2 nanodots‐based nanoplatform is promising for elevating the oxygen level in tumor microenvironments to overcome hypoxia limitations for high‐performance cancer therapy. A MnO2 nanodots loaded nanoplatform reacting with endogenous acidic H2O2 to increase the oxygen concentration is demonstrated, overcoming hypoxia in tumors and simultaneously enhancing the efficiency of chemical and photodynamic therapy. The produced biocompatible nanoplatform exhibits a highly effective therapeutic effect in vitro and can eliminate the tumor in vivo.