Here, ACSL4 depletion decreased phosphorylation of ERK leading to downregulation of phosphorylation of c-Myc serine 62 (pS62) and upregulation of FBW7 in Huh7 cells, which was reversed by ERK specific inhibitor SCH772984, indicating that ERK signaling has a key role in ACSL4-mediated c-Myc stability in HCC. Here, ACSL4 is linked to hepatocellular carcinoma.