Although NRF2’s role in regulating key signaling processes of ferroptosis is recognized, and extensive research links NRF2 with the proliferation, invasion, and migration of ESCC as an oncogenic factor, the specific mechanism of NRF2 in modulating ferroptosis to confer radiotherapy resistance in ESCC remains unexplored. Here, NFE2L2 is linked to esophageal squamous cell carcinoma.