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Tumorigenesis is closely related to defects in DNA damage response (DDR), which plays an important role in maintaining genomic integrity. The DDR process includes DNA damage recognition, cell cycle checkpoint pathway activation, and DNA damage repair. On the one hand, defects in DDR increase the instability of the cellular genome, which ultimately leads to tumorigenesis. On the other hand, tumor therapy can take advantage of DDR defects to induce apoptosis by causing damage to tumor cells, thus achieving therapeutic goals. Tumor immunotherapy is an emerging method of tumor treatment that attacks and kills cancer cells by inhibiting negative regulatory factors, enhancing the ability of immune cells to recognize antigens on the surface of tumor cells and activating the patient's own immune system. Recent research evidence suggests that DDR inhibition enhances antitumor immune responses and acts in synergy with immunotherapy. This review describes the different categories of DNA damage, their corresponding DNA damage repair pathways, the antitumor mechanisms of action targeting DDR inhibition, and the prominent contributions of these mechanisms to the immunotherapeutic response. By exploring recent advances in the interactions between targeted DDR and immunotherapy, this review provides novel therapeutic insights into the treatment of DNA damage-associated cancers as well as the development of combination immunotherapy.