Sun et al. (2016) revealed the role of the p62-Keap1-NRF2 pathway in ferroptosis in HCC cells. Inhibiting the expression of NRF2 genetically or pharmacologically enhanced the anti-tumor effect of erastin and sorafenib by upregulating the levels of iron and ROS. Recently, Sun et al. (2021) found that QSOX1 could also inhibit NRF2 activation to promote sorafenib-induced ferroptosis. Besides, triggering the AMPK/SREBP1 pathway to inhibit the transcription of BCAT2 contributes to ferroptotic death in HCC (Wang et al., 2021). This evidence concerns the gene NFE2L2 and hepatocellular carcinoma.