Our examination of Sirt6-LKO mice at about two years of age clearly detected spontaneous HCC formation in 6 out of 7 (86%) mutant mice, which is more than triple as much as the control (Figs. 6A,B and EV5A), suggesting that Sirt6 is a tumor suppressor in liver cancer. This evidence concerns the gene SIRT6 and hepatocellular carcinoma.