Objective：Previous genome - wide association study（GWAS）has identified that rs2252004 was associated with the susceptibility of prostate cancer. This study was aimed to investigate the molecular biological mechanisms underlying the effect of rs2252004 on tumorigenesis of prostate cancer. Methods：We obtained the genotype，methylation and gene expression data from The Cancer Genome Atlas（TCGA）database. The relationships between rs2252004 genotype（0，1，or 2）and the β-value or proportion of methylation at each CpG site（within 500 kb of rs2252004）and the expression level of involved genes were evaluated via linear regression. Results：The results showed that rs2252004 was significantly associated with the methylation level of three CpG cites located in FGFR2（cg25294906，P=0.031；cg03552039，P=0.042；cg16499947，P=0.049，respectively）. Furthermore，the expression of FGFR2 remarkably differed between 50 paired prostate tumors and adjacent normal tissues（P=9.3×10-11）. Besides，individuals carrying rs2252004 GT genotypes were significantly associated with decreased expression of FGFR2 than those with GG genotypes（P=0.007）. We also observed a notable different expression of FGFR2 between GT/TT genotype and GG genotype individuals（P=0.006）. Conclusion：Altogether，our results suggest that rs2252004 may regulate the methylation level of FGFR2，which contributes to influence FGFR2 expression，thus be involved in the tumorigenesis of prostate cancer.