Single nucleotide polymorphisms in miRNA binding sites (miR-SNPs) are associated with cancer risk. We assessed the relationship between five miR-SNPs in the 3 ' untranslated region (3 '-UTR) ofRYR3(rs1044129),KIAA0423(rs1053667),C14orf101(rs4901706),GOLGA7(rs11337), andKRT81(rs3660) and the risk of breast cancer (BC). The CC genotype of rs3660 located in the 3 '-UTR ofKRT81was identified for its association with lower BC risk (odds ratio, 0.093; 95% confidence interval, 0.045-0.193;p = 0.000). Immunnochemical analysis and Renilla luciferase reporter assays indicated that the CC genotype ofKRT81was associated with lower expression ofKRT81(p < 0.05). The subsequently functional analysis showed that knockdown theKRT81could inhibit proliferation and promote apoptosis of the MDA-MB-231 BC cells (p < 0.05) with monocyte chemotactic protein-1 (MCP-1) deregulation. Meanwhile,KRT81overexpression could promote the proliferation and inhibit the apoptosis of MCF-7 BC cells (p < 0.05). Our data demonstrated that theKRT81expressional change modulated by rs3660 miR-SNP could modify the carcinogenesis of BC, therebyKRT81would be a new target for BC treatment.