Abstract  Objective  To investigate the relationship between MTHFR C677T gene polymorphisms, the expression and promoter methylation status of tumor-suppressor gene SFRP1 in renal clear cell carcinoma.Methods   A casecontrol study consisting of 38 renal cancer cases and 38 controls matched on sex and age was conducted. MTHFR gene C677T polymorphisms were detected by PCRRFLP technology, Realtime PCR was used to detect the mRNA expression of SFRP-1 , then the status of the SFRP-1 promoter methylations in the tumors was detected using a methylation specific PCR (MSP).Results   Promoter hypermethylation was frequently detected in renal cancer tissues that expressed lower level or lost expression of SFRP-1 gene in 677CC genotypes patients, SFRP-1 methylation and expression and MTHFR C677T gene polymorphism has obvious correlation.Conclusions  MTHFR gene polymorphisms could effect methylation status and regulate its expression of SFRP-1 gene, it probably plays an important role in process of occurrence and development in renal cell carcinoma.