Taken together, we show that two exonic SNPs of H19, rs2839698 and rs3741219, render individuals more susceptible to HCC, whereas upstream or intronic SNPs of H19 (rs2107425 and rs3024270) exhibit protective effects on the development of liver cancer, revealing a functional complexity of H19 gene polymorphism in governing hepatocarcinogenesis. Here, H19 is linked to hepatocellular carcinoma.