Oxygen (O-2) plays a critical role during photodynamic therapy (PDT), however, hypoxia is quite common in most solid tumors, which limits the PDT efficacy and promotes the tumor aggression. Here, a safe and multifunctional oxygen-evolving nanoplatform is costructured to overcome this problem. It is composed of a prussian blue (PB) core and chlorin e6 (Ce6) anchored periodic mesoporous organosilica (PMO) shell (denoted as PB@PMO-Ce6). In the highly integrated nanoplatform, the PB with catalase-like activity can catalyze hydrogen peroxide to generate O-2, and the Ce6 transform the O-2 to generate more reactive oxygen species (ROS) upon laser irradiation for PDT. This PB@PMO-Ce6 nanoplatform presents well-defined core-shell structure, uniform diameter (105 +/- 12 nm), and high biocompatibility. This study confirms that the PB@PMO-Ce6 nanoplatform can generate more ROS to enhance PDT than free Ce6 in cellular level (p < 0.001). In vivo, the singlet oxygen sensor green staining, tumor volume of tumor-bearing mice, and histopathological analysis demonstrate that this oxygen-evolving nanoplatform can elevate singlet oxygen to effectively inhibit tumor growth without obvious damage to major organs. The preliminary results from this study indicate the potential of biocompatible PB@PMO-Ce6 nanoplatform to elevate O-2 and ROS for improving PDT efficacy.