Specifically, p62 was accumulated in autophagy-defective cells and interacts with Keap1 on the NRF2-binding site to disrupt the ubiquitination of NRF2 mediated by CRL3Keap1, resulting in the hyperactivation of NRF2, which may contribute to hepatoma development [136–138]. This evidence concerns the gene NFE2L2 and hepatocellular carcinoma.