Notably, the regulation of ferroptosis by the PI3K/AKT pathway may be tissue-specific, and the STAT3-dependent regulatory pattern identified in this study complements the mechanism of direct phosphorylation of GPX4 by AKT reported in hepatocellular carcinoma, highlighting the complexity and context-dependence of the pathway network in the regulation of cell death. Here, GPX4 is linked to hepatocellular carcinoma.