A multifunctional PCA/DOX/MoS hydrogel was designed and prepared for chemotherapy/photothermal therapy/photodynamic therapy of 4T1 tumor, and the immune responses triggered by photothermal and photodynamic effect of MoS nanosheet in the hydrogel were also studied. Positively charged DOX and negatively charged PCA were loaded on the surface of MoS nanosheet through layer-by-layer method to prepare hybrid PCA/DOX/MoS nanoparticles. PCA/DOX/MoS nanoparticles were dispersed in PCA hydrogel to prepare PCA/DOX/MoS hydrogel. 2D MoS nanosheet in the hydrogel was simultaneously utilized as photothermal agent and photodynamic agent for the generation of hyperthermia and reactive oxygen species, respectively. This PCA/DOX/MoS hydrogel was injectable and possessed excellent biocompatibility. The results of in vivo tumor-bearing mice experiments showed that a remarkably enhance tumor inhibition was observed by the combination of chemo-photothermal-photodynamic therapy compared with photothermal therapy, photodynamic therapy, or chemotherapy alone. In addition, the results of in vivo therapy exhibited that the PCA/DOX/MoS hydrogel with laser irradiation could activate antitumor immune effects to suppress the growth of primary 4T1 breast tumors and distal lung metastatic nodules. Therefore, these results demonstrated that the PCA/DOX/MoS hydrogel was promising to be utilized in antitumor immunity therapy triggered by photothermal therapy and photodynamic therapy for malignant tumor.