Prostaglandin D2 (PGD2) is a biologically active substance with important roles in a variety of physiological and pathological processes, and it exerts its biological functions mainly through Prostaglandin D2 synthase (PGDS), which is closely related to inflammation and immune regulation. Recent studies based on animal models have found that PGD2 and its synthase, PGDS, are able to inhibit tumor cell proliferation, induce apoptosis, suppress migration and invasion, further regulate the tumor immune microenvironment to affect the immunotherapy of tumors, demonstrating a good tumor therapeutic potential. In this paper, we reviewed the biological properties of PGD2 and its synthase, focused on its role in the immunotherapy of tumor animal models, and explored the immunotherapeutic efficacy of PGD2 and its synthase by promoting immune cell infiltration in the tumor microenvironment, which is expected to provide a new target for tumor therapy.