Objective:This study aims to clarify the effects of H19 genetic variant rs2839698,rs217727,rs3741216 and rs3741219 on renal cell carcinoma(RCC) susceptibility and prognosis. Methods:We conducted this two-stage case-control study with a total of 1 014 RCC cases and 1 063 controls since May 2004. Total 298 RCC cases in the first stage had complete follow-up data available. Genotyping was performed using TaqMan real-time polymerase chain reaction assays. Odds ratio(OR)and 95% confidence interval(CI) were calculated to evaluate the association between H19 polymorphism and RCC risk and clinical characteristics. Kaplan-Meier method was utilized to assess the survival of H19 polymorphisms. Hazard ratio(HR)and 95%CI were calculated by COX regression model to discover whether genotypes,TNM and grade were the independent prognostic factors. Results:Compared with the H19 rs2839698 CC genotype,the variant genotypes(CT/TT)were significantly associated with increased risk of RCC(P=0.012,OR=1.13,95% CI=1.02-1.55). Besides,patients with variant genotypes(CT/TT)were more likely to develop large tumor(P=0.003,OR=1.35,95% CI=1.10-1.73)and advanced disease(P=0.010,OR=1.63,95% CI=1.08-2.21);and had a significantly unfavorable 5-year survival than those with the rs2839698 CC genotype(CT/TT vs. CC:Log-rank P=0.027,HR=2.24,95%CI=1.10-4.59). Conclusion:The results suggested that H19 rs2839698 variant may be a genetic predictor of susceptibility and mortality of RCC. The precise functional impact of the variant on H19 still needs further experimental validation.