Spinal cord injury (SCI) is a central nervous system disease with high morbidity, disability, and mortality. A series of pathological and physiological changes after SCI, including oxidative stress, can promote further deterioration of the microenvironment at the injury site, resulting in impaired neurological function. Nuclear factor E2related factor 2 (Nrf2) is highly correlated with oxidative stress, suggesting that targeting the regulation of Nrf2 and alleviating oxidative stress may be an effective treatment for SCI. We consider the application of Nrf2 in post-SCI oxidative stress, based on the occurrence of oxidative stress after SCI and the relationship between oxidative stress and Nrf2. We also summarize the strategies for targeting and regulating Nrf2, including genes, non-coding RNAs, and drugs, with the aim of providing new ideas for targeted therapy of SCI.