Upregulation of HMOX1 expression has been shown to play a cytoprotective role138 and to increase the resistance of HCC cells to ferroptosis mediated by the p62-KEAP1 (Kelch-like ECH-associated protein 1)-NRF2 (nuclear factor erythroid-2-related factor 2) pathway.34 On the other hand, high HMOX1 expression can also be toxic due to high levels of ferrous iron,139 which in turn accelerates the Fenton reaction, particularly in the context of insufficient levels of free radical scavengers. This evidence concerns the gene NFE2L2 and hepatocellular carcinoma.