We found that the level of galactosylation and B-cell B4GALT1 expression increased in the male mice HCC model, and that the B-cell-specific ablation of B4GALT1 inhibited the development of DEN/CCl4-induced HCC and reversed the changes observed in the galactosylation level. Here, B4GALT1 is linked to hepatocellular carcinoma.