Although great strides have been made in the management and treatment of hepatocellular carcinoma (HCC), its prognosis is still poor yielding a high mortality. Immunotherapy is recommended for treating advanced HCC, but its efficiency is hampered because of hepatic immunosuppression. Stimulator of interferon genes (STING) pathway, serving as a critical cytoplasmic DNA-sensing process, is reported to initiate the antitumor immune response, and link the innate immunity to the adaptive immune system. Radiotherapy has been well acknowledged to induce destruction and release of tumor-derived DNA into the cytoplasm, which then activates the cGAS-STING pathway. On this basis, radiotherapy can be used as a sensitizer for immunotherapy, and its combination with immunotherapy may bring in changes to the suboptimal efficacy of immune checkpoint inhibitor monotherapy. In this review, we summarized the roles of cGAS-STING pathway in regulation of radiotherapy combined with immunotherapy for treating HCC.

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