We verified that 3 of the 16 included SNPs in the DMR upstream loci of H19 gene, namely rs4930101, rs11042170, and rs2735970, especially in the combined risk genotypes of the 3 SNPs were remarkably associated with an increased advanced CRC risk, environmental factors, and the clinical outcomes in the advanced CRC patients with body weight ≥ 61 kg, smoking, and first-degree family history of cancer. Here, H19 is linked to cancer.