Sorafenib exerts antitumor effects by targeting multiple kinases (e.g., VEGFR, PDGFR, and RAF kinases) as well as xCT, and by activating PI3K and AMPK pathways implicated in sorafenib resistance [6, 18]; however, it is largely unknown whether sorafenib induces macropinocytosis in HCC and whether macropinocytosis functions as an alternative pathway for acquisition of cysteine to prevent sorafenib-induced ferroptosis and reduce susceptibility to sorafenib. Here, SLC7A11 is linked to hepatocellular carcinoma.