Nowadays, chemotherapy is a common clinical treatment for cancer, but it still faces many limitations and challenges. Therefore, the combination of chemotherapy and other treatments often enhances the effectiveness of treatments. Herein, an injectable hydrogel of PCARGD/Cu/DOX based on Cu, hydrophilic doxorubicin (DOX), and genetically engineered polypeptide PCARGD was prepared. First, Cu was attached to the histidines in the PCARGD polypeptide by the coordination reaction to form PCARGD/Cu hydrogel, then the PCARGD/Cu/DOX hydrogel was prepared by encapsulating the DOX into the PCARGD/Cu hydrogel. The results of scanning electron microscopy showed that the PCARGD/Cu/DOX hydrogel displayed loose porous morphology. , reactive oxygen species production results showed that the PCARGD/Cu/DOX hydrogel could continuously produce ·OH in the presence of HO. MTT results showed that the PCARGD/Cu/DOX hydrogel had a good inhibitory effect on cell activity. Flow cytometry further confirmed the antitumor effect of the PCARGD/Cu/DOX hydrogel. experiment results showed that the tumor volume of mice treated with the PCARGD/Cu/DOX hydrogel was significantly inhibited compared with control groups, which was due to the combination of chemodynamic and chemotherapy. The results of body weight and blood analysis of mice showed that the PCARGD/Cu/DOX hydrogel possessed good biocompatibility.