Knockdown of Nrf2 enhanced the decrease in cell viability induced by erastin and sorafenib in HCC cells, with increased defining events of ferroptosis (e.g., GSH depletion, lipid ROS accumulation, and increased level of iron), which could be reversed by inhibitors of ferroptosis other than inhibitors of apoptosis and necroptosis. This evidence concerns the gene NFE2L2 and hepatocellular carcinoma.