The development of effective nanoplatforms is extremely necessary for cancer therapy. Herein, we prepared polydopamine (PDA) and ammonium bicarbonate (NH₄HCO₃) coated and doxorubicin (Dox) loaded hollow cerium oxide (CeO₂) NPs (PDAC NPs), which showed excellent synergistic effect for photothermal therapy, chemotherapy and chemodynamic therapy. Under near infrared laser irradiation, PDA shell could absorb the incident light and convert it into heat, which could not only kill tumor cells with hyperthermia, but also trigger the decomposition of NH₄HCO₃ into gaseous carbon dioxide and ammonia, leading to the destroy of PDA shell. The leakage of PDA further accelerated Dox release and exposed CeO₂ surface, in which Dox could enter into cell nucleus to induce chemotherapy, and CeO₂ could catalyze cellular hydrogen peroxide into hydroxyl radical to present chemodynamic therapy. In fact, PDAC NPs showed an excellent therapeutic efficacy both in vitro and in vivo. This design provides a new strategy for synergistic tumor therapy.