Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) is a transcription factor that can regulate downstream target gene expression. Kelch-like ECH-associated protein 1 (Keap1) negatively regulates Nrf2 activation and translocation to target its 26S proteasomal degradation. It has been widely reported that the Keap1/Nrf2 pathway is associated with tumorigenesis, chemotherapy resistance and progression and development of non-small cell lung cancer (NSCLC). High expression of Nrf2 and low abundance of Keap1 contribute to the abnormalities and unrealistic treatment prognosis of NSCLC. Therefore, elucidating the role and potential mechanism of Nrf2 in NSCLC is essential for understanding tumorigenesis and for the development of strategies for effective clinical management. Here, we summarize current knowledge about the molecular structure and biological function of Nrf2, and we discuss the roles of Nrf2 in tumorigenesis, which will further provide a possible therapeutic strategy for NSCLC.