Objective: The exploration of the synergistic anti-tumor effects and mechanisms of doxorubicin(DOX)-loaded copper-based metal-organic framework (Cu-MOF@DOX) nanoplatform for cancer chemodynamic therapy. Methods: The nanoscale Cu-MOF was prepared by a facile stirring method, which acted as the nanocarrier for loading DOX. Transmission electron microscope (TEM) was used to characterize these Cu-MOF. CCK-8 assays were used to investigate the cytotoxicity of Cu-MOF@DOX againstoral cancer cells. Confocal laser scanning microscopy (CLSM) was used to study the cellular uptake of Cu-MOF and the generation of intracellular reactive oxygen species (ROS).The depletion of glutathione (GSH) in cancer cells by Cu-MOF@DOX was investigated by a GSH assay kit. Western blotting analysis was used to investigate the expression of BAX and Bcl-2of Cu-MOF@DOX-treated cancer cells. Results: TEM image showed the uniform size distribution and good dispersibility of these Cu-MOF. Cu-MOF@DOX has a significant anti-tumor effect in a dose-dependent manner (P<0.05).Compared with DOX alone, both Cu-MOF and Cu-MOF@DOX could deplete GSH (P<0.001). The DOX in Cu-MOF@DOX could be more effective uptaken by cancer cells and produced large amounts of ROS. Conclusions: Cu-MOF@DOX can effectively induce apoptosis of oral cancer cells through the synergistic effects of chemodynamic therapy and chemotherapy, which held good potential in oral cancer therapy.