Spinal cord injury (SCI) is a central nervous system disease with high morbidity, high disability and high mortality. A series of pathological and physiological changes after SCI, such as oxidative stress, will promote the further deterioration of the microenvironment at the site of injury, resulting in impaired neurological function. Nuclear factor E2-related factor (Nrf2) is a factor highly correlated with oxidative stress, so targeting the regulation of Nrf2 and alleviating oxidative stress may be one of the treatments for SCI. This article discusses 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, and summarizes the strategies for targeting and regulating Nrf2, such as genes, non-coding RNAs and drugs, in the hope of providing new ideas for targeted therapy of SCI.