Fas and Fas ligand system is one of the key components in the apoptotic pathway.Fas -1377G>A,-670A>G and FasL-844T>C polymorphisms affecting the genes expression are widely investigated in breast cancer.Additionally, the migration and invasion inhibitory protein (MIIP) is paid close attention in recent years.To reveal the effect ofFas, FasL and MIIP (-167A>G) polymorphisms to the occurrence of breast cancer risk, herein 439 breast cancer patients and 439 controls were enrolled in this study.The genotypes were detected by MassARRAY, and the estrogen receptor, progesterone receptor, CerbB-2 were determined by immunohistochemistry.From the 439 patients, 22 breast cancer and adjacent normal tissues were collected to detect the mRNA level of Fas by real-time PCR, and soluble Fas and FasL concentrations of 180 patients were detected by enzyme-linked immuno sorbent assay.The results showed Fas-1377GA, AA and GA/AA genotypes were associated with decreased breast cancer risk, the same as Fas-670AG, GG and AG/GG genotypes.For FasL-844T>C polymorphism, TC and CT/TT genotype were associated with decreased breast cancer risk.Furthermore, haplotype analysis indicated Fas-1377G/-670A was associated with increased breast cancer risk, while-1377A/-670A with an opposite effect.The gene-gene interaction analysis of Fas and FasL polymorphisms revealed Fas-1377GA/AA (Fas -670AG/GG) and FasL-844CC or TC/TT genotypes associated with decreased breast cancer risk.Meanwhile, it was found that-1377GG genotype was associated with higher sFas concentration than other genotypes, the same as-670AA genotype.As for MIIP-167A>G polymorphism, AG and AG/GG genotypes were associated with decreased breast cancer risk.These findings indicate that Fas, FasL and MIIP polymorphisms can affect breast cancer risk, and Fas polymorphisms effect breast cancer risk by regulating the sFas concentration.Due to some limitations of this study, the conclusion deserves further elucidation in larger and multi-ethnic populations.