Objective:To investigate the association between two polymorphisms of BARD1 gene and the susceptibility of breast cancer in a Chinese population. Methods:Genotyping were performed using PCR-restriction fragment length polymorphism(PCR-RFLP) assay in 422 histological-confirmed breast cancer cases and 476 age frequency-matched cancer-free controls. Results:The genotypes distribution of the BARD1 Pro24Ser(rs1048108) and Arg378Ser(rs2229571) polymorphisms were significantly different between cases and controls. Multivariate logistic regression analysis revealed that variant genotypes of Pro24Se polymorphism(CT/TT) and heterozygotes of Arg378Ser polymorphism were both associated with a significantly decreased risk of breast cancer(adjusted OR=0.64,95%CI=0.49-0.84;adjusted OR=0.54,95%CI= 0.33-0.86,respectively) compared with the wild-type genotype(24CC and 378GG). Furthermore,these two polymorphisms may have joint effect on breast cancer risk. Individuals with more than one protective allele showed a significantly decreased risk compared with those with 0-1 protective allele(adjusted OR=0.67,95% CI=0.51-0.87). Stratified analysis showed that the protective effect of Pro24Ser polymorphism was more evident in subjects with age less than 52,premenopausal status,without family history of cancer and Arg378Ser variant genotypes carriers. Conclusion:Pro24Ser(rs1048108)and Arg378Ser(rs2229571) polymorphisms of BARD1gene were associated with a significantly decreased risk of breast cancer. And these two polymorphisms may jointly affect individuals’ susceptibility. More rigorous laboratory studies and larger epidemiological studies with ethnically diverse populations are warranted to confirm our findings.