Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality. Radiotherapy technology is a common treatment modality that can be used in all stages of HCC. However, in some cases, radiotherapy fails in clinical practice mainly because of the patient's resistance to radiotherapy, creating a bottleneck for future breakthroughs. HCC radiosensitivity is primarily related to DNA double-strand break repair, cellular autophagy, cell cycle, cellular metabolism, and hypoxic environmental regulators. Therefore, a comprehensive understanding of its molecular mechanisms will be of immense importance in reversing HCC radioresistance. In this review, we provide a comprehensive overview of the mechanism of action of radiotherapy on HCC, the cellular and molecular basis of radiation resistance in HCC, related treatment modalities, and future prospects.
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