In summary, our results reveal the specific mechanism by which Cav-1 exerts an oncogenic effect in HCC cells, as based on enhanced glycosyltransferase expression and O-fucosylation-induced tumor metastasis, suggesting that inhibiting Pofut1 or other glycosyltransferases may constitute an optimal strategy for treating metastatic HCC. Here, POFUT1 is linked to hepatocellular carcinoma.