With the rapid development of photo-responsive nanomaterials, photo-triggered therapeutic strategies such as photothermal therapy (PTT) and photodynamic therapy (PDT) have been new alternatives to current cancer therapeutic methods. Herein, we have fabricated oxygen vacancy-engineered BaTiO₃ (BTO-Ov) nanoparticles (NPs) for near-infrared (NIR) light-triggered PTT, PDT, and catalytic therapy cooperatively for significantly improving cancer therapy. Compared to pristine BaTiO₃ nanoparticles, BTO-Ov has stronger NIR light absorption and narrower band gap structure, which results in superior photothermal conversion and superoxide radical generation capabilities through PTT and PDT. Meanwhile, due to the existence of Ti³⁺, BTO-Ov also exhibits peroxidase (POD)-like activity to produce hydroxyl radical under tumor environment, which can be further improved under 808 nm light irradiation. Both in vitro and in vivo results demonstrate that such a multifunctional therapeutic nanoplatform can achieve a high therapeutic efficacy triggered by a single NIR light irradiation. The defect engineering strategy can be used as a general approach to fabricate multifunctional cancer therapeutic nanoplatform.