Our results show hepatic Nrf1 is important for preventing MASH-linked hepatocyte proliferation, liver inflammation, and HCC, that actions by Nrf1 and Nrf2 synergistically reduce hepatic lipid storage, and that the Nrf2-inducing drug bardoxolone alleviates liver inflammation and fibrosis. Here, NFE2L2 is linked to hepatocellular carcinoma.