To evaluate whether the genetic variants in H19 influence the risk of oral squamous cell carcinoma (OSCC) in a Chinese population, a case-control study was conducted to analyze four functional single nucleotide polymorphisms (SNPs) in H19. The cohort comprised of 444 OSCC cases and 984 healthy controls, and the study further evaluated the biological effect by bioinformatics prediction and functional experiments. This evidence concerns the gene H19 and oral cavity squamous cell carcinoma.