Reactive oxygen species (ROS)-mediated cell apoptosis has been a significant strategy for tumor oxidative damage, while tumor hypoxia is a major bottleneck for efficiency. Here, a novel TiO-porphyrin nanosystem (FA-TiOPs) is designed by encapsulating TiO-porphyrin (TiOP) in folate-liposome. The nanosysytem can photocatalyze H2O and tumor-overexpressed H2O2, in situ generating sufficient ROS. TiOP can photosplit water to produce center dot OH radical, H2O2, and O-2. Generated O-2 not only conquers the hypoxia of tumor environment but also can be further excited by TiOP to O-1(2) for killing tumor cells. Density functional theory calculations indicate that high energy in excited state (S-1) of TiOP and narrow gap energy between S-1 and the triplet excited state (T-n) might contribute to the efficient photocatalytic action. Moreover, the generated and overexpressed H2O2 in tumors can also be photocatalyzed to generate O-1(2) especially in acid condition, helpful to specific anticancer effect while harmless to normal tissues. This research might pave a new way to bypass the hypoxia-triggered problem for cancer therapy.