Given the importance of this pathway in carcinogenesis, ethnic differences and the discrepancies in previous studies, the present case-control study was conducted to define the association between the one-carbon metabolism pathway genes polymorphisms and the ccRCC risk in Chinese population, through testing the polymorphism in six key genes (CBS, MTHFR, MTR, MTRR, SHMT1, and TYMS) in this pathway. This evidence concerns the gene MTHFR and nonpapillary renal cell carcinoma.