In this work, we demonstrate that when PRDX6 is eliminated using CRISPR/Cas9 technology, SNU475 hepatocellular carcinoma cells greatly modify their lipid composition causing a drastic decrease in DHA, an increase in TAGs that accumulate in LDs, a likely disassembly of lipid rafts and a disruption of plasmalogens homeostasis resulting in a higher sensitivity to the induction of ferroptosis. This evidence concerns the gene PRDX6 and hepatocellular carcinoma.