Objective:Foxp3,the main regulator of Treg (regulatory T) cells, is down-regulated in breast carcinoma and other cancers. The rs2294021 Foxp3 polymorphism contributes to Foxp3 down-regulation, thereby weakens its tumor suppressing activity. The aim of our study was to evaluate the potential influence of Foxp3 polymorphism on breast cancer, we conducted a case-control study in Han Chinese women. Methods: Foxp3 genotyping was conducted in 677 breast carcinoma patients and 828 age-frequency matched cancer-free controls. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Experiment data was analyzed using Chi-square test and SPSS software. Results: The T/C genotype was found to be significantly associated with increased risk of breast carcinoma occurrence (OR = 1.462; 95% CI 1.165-1.833, P = 0.001) compared with the T/T or C/C (OR 1.143; 95% CI 0.838-1.559, P = 0.397) genotype. The increased risk for breast carcinoma related to heterozygous genotype was more pronounced in subjects over 50 years (OR 1.631; 95% CI 1.116-2.383, P = 0.011). No significant association was found between the polymorphism and the ER/PR status, metastasis or tumor stage of breast cancer. Conclusion: Our findings suggest that rs2294021 Foxp3 polymorphism may be a potential contributor for development of breast carcinoma in Han Chinese women. The target of Foxp3 down-regulation, thereby weakens its tumor suppressing activity. The aim of our study was to evaluate the potential influence of Foxp3 polymorphism on breast cancer, we conducted a case-control study in Han Chinese women. Methods: Foxp3 genotyping was conducted in 677 breast carcinoma patients and 828 age-frequency matched cancer-free controls. Results: The T / C genotype was found to be significantly associated with increased risk of breast carcinoma occurrence (ORF-PCR) = 1.462; 95% CI 1.165-1.833, P = 0.001) compared with the T / T or C / C (OR 1.143; 95% CI 0.838-1.559, P = 0.397) genotype. o heterozygous genotype was more pronounced in subjects over 50 years (OR 1.631; 95% CI 1.116-2.383, P = 0.011). No significant association was found between the polymorphism and the ER / PR status, metastasis or tumor stage of breast cancer. Conclusion: Our findings suggest that rs2294021 Foxp3 polymorphism may be a potential contributor for development of breast carcinoma in Han Chinese women.