Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths, and cases are on the rise due to increased prevalence of metabolic syndromes and alcohol consumption. HCC has a poor prognosis and is challenging to treat due to the immune-tolerant nature of the liver and resulting immunosuppressive tumor microenvironment (TME). Radiotherapy has emerged as an effective HCC treatment that is able to remodel the TME of HCC tumors by inducing dsDNA breaks that activate the cGAS-STING pathway and downstream anti-tumor immune response. However, numerous mechanisms of radioresistance can limit radiotherapy efficacy, including suppression of radiation-induced cGAS-STING activation and, paradoxically, the immunosuppressive effects that can arise from sustained or context-dependent cGAS-STING signaling. In this review, we will first examine how underlying conditions such as liver matrix stiffness, gut bacteria dysbiosis, and tumor mutations can impair STING activation and how novel STING agonists and DNA damage response (DDR) inhibitors can promote radiosensitivity by enhancing STING activation. We will further discuss how immunotherapy can synergize with radiotherapy by mitigating the immunosuppressive effects of STING activation as well as how artificial intelligence can be integrated to improve HCC patient outcomes.