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BACKGROUND: Tissue damage induced by radioactive ionizing radiation is one of the serious complications of radiotherapy. Activation of endogenous antioxidative stress response through nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/antioxidant responsive element (ARE) signaling pathway has shown preventive and therapeutic effects on radiation-induced tissue injuries. OBJECTIVE: To explain the preventive and therapeutic mechanisms of Nrf2/ARE signaling pathway on radiation-induced injuries, and provide new ideas for exploring the treatment and prevention strategies of radiotherapy complications. METHODS: PubMed, Web of Science, CNKI, WanFang and VIP databases were searched using the keywords of “radiation injury, radiation-induced tissue injury (intestine, liver, tongue, lung, bone marrow, skin, hematopoietic system, nervous system, circulatory system), radiation damage, radiation syndrome, Nrf2” in Chinese and English, respectively. A total of 67 literatures were finally included and reviewed. RESULTS AND CONCLUSION: Radiation-induced injury is damage to tissues caused by the intramolecular bond homolysis of ionizing radiation biomolecules that lead to an increase in cytotoxic free radicals and reactive oxygen species. TheNrf2/ARE signaling pathway is an important endogenous antioxidant defense mechanism in the body. By enhancing the expression of antioxidant response elements, it can reduce DNA damage, promote damaged DNA repair, and inhibit radiation-induced cell apoptosis. Therefore, the Nrf2/ARE signaling pathway is of great significance for the prevention and correction of cellular redox imbalances including radioactive tissue damage. Current studies have found that the activation of Nrf2/ARE signaling pathway has two sides. On the one hand, the application of Nrf2/ARE signaling pathway activator cannot only prevent tissue loss caused by radiotherapy, but also induce the repair of damaged tissue after radiotherapy. On the other hand, the long-term and chronic activation of the Nrf2/ARE signaling pathway caused by various reasons may reduce the sensitivity of malignant tumors to radiotherapy and chemotherapy. Therefore, the Nrf2 /ARE signaling pathway has potential as a new strategy for the prevention and treatment of radiotherapy complications; however, whether it can be applied in clinical practice still needs further exploration and research. [ABSTRACT FROM AUTHOR]