Abstract: Objective To investigate the expression of nuclear factor erythroid 2-related factor-2 (NRF2) in esophageal cancer and its relationship with the radiotherapy sensitivity in esophageal cancer patients. Methods A total of 42 esophageal cancer patients who were admitted from January 2018 to December 2018 were enrolled. Their levels of NRF2 in specimens were detected by immunohistochemistry, and the relationship between NRF2 expression in cancer and adjacent non-cancer tissues and the sensitivity of radiotherapy, clinical stage, and recent effectiveness was analyzed. Results There were 26 patients in the radiation-sensitive group and 16 patients in the radiation-resistant group, with a radiation sensitivity of 61.9%. The level of NRF2 in cancer tissues was significantly higher than that in adjacent non-cancer tissues (P<0.05), and the positive and strongly positive percentages were lower in the radiation-sensitive group than that in the radiation-resistant group (P<0.01).The expression of NRF2 in adjacent non-cancer tissues was 14.3% (6/42). Conclusions There is a significant correlation between NRF2 expression and radiation sensitivity in esophageal cancer patients. Detection of NRF2 expression in cancer and adjacent non-cancer tissues in esophageal cancer patients has the potential to screen out patients who are sensitive to radiotherapy for better prognosis.