In line with the in vitro cell assays, we found Prelid2 knockdown markedly decreased the tumor volume and weight of HCC xenograft (P < 0.01, Additional file 1: Fig. S6b-f), indicating that Fbxl6 elevation synergizes with KrasG12D to drive HCC tumorigenesis via the upregulation of Prelid2. Here, FBXL6 is linked to hepatocellular carcinoma.