In the current study, we investigated the associations of the TCF21 polymorphisms (rs2327429 T > C, rs2327430 T > C, rs2327433 A > G, rs12190287 C > G, rs7766238 G > A, rs4896011 T > A) with the risk of breast cancer in Chinese women, and found that the TCF21 rs12190287 polymorphism in hsa-miR-224 binding site was significantly associated with the reduced risk of breast cancer under all comparison models. This evidence concerns the gene TCF21 and breast cancer.