T-cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3) is a novel transmembrane protein that is involved in the regulation of T-helper 1 (Th1)-cell-mediated immunity. This study was undertaken to investigate the association of TIM-3 polymorphisms with susceptibility to renal cell carcinoma (RCC) in the Chinese population. Blood was collected from 322 RCC patients and 402 healthy controls. Three polymorphisms in the TIM-3 gene (-1516G/T, -574G/T, and +4259T/G) were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Results showed that the -574G/T and +4259T/G polymorphisms were significantly increased in the RCC cases (odds ratio [OR] = 2.77, 95% confidence interval [CI], 1.42-5.39, p = 0.002 and OR = 3.22, 95% CI, 1.64-6.35, p<0.001). When analyzing the haplotypes of TIM-3 polymorphisms, TTG (-1516, -574, and +4259) revealed a significant correlation with RCC (OR = 3.55, 95% CI, 1.13-11.2, p = 0.033). In addition, the prevalence of +4259T/G polymorphism was higher in RCC cases with metastasis than in those without metastasis (7.4% vs. 3.5%, p = 0.041). These results suggest that polymorphisms in the TIM-3 gene are new risk factors for RCC and that TIM-3 may play important roles in regulating the prognosis of this disease.