Our results confirm beneficial effects of the Nrf2 inducer bardoxolone to alleviate liver inflammation and fibrosis, establish a robust synergistic role for Nrf1 and Nrf2 to reduce hepatic lipid storage, and demonstrate that hepatocyte Nrf1 plays a greater physiological role than Nrf2 in preventing HCC. This evidence concerns the gene NFE2L2 and hepatocellular carcinoma.