It is well established that P62 can protect ROS-rich HCC-initiating cells from oxidative stress-induced cell death by activating the Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) and the mechanistic Target of Rapamycin Complex 1 (mTORC1) pathways thereby contributing to its persistence-elevated levels of p62 have been observed in HCC progenitor cells and are commonly found in most chronic liver diseases that progress to HCC. Here, NFE2L2 is linked to hepatocellular carcinoma.