Abstract Background Breast cancer (BC) is common cancer caused by environmental factors and genetic ones. Previous evidence has linked gene MAGUK P55 Scaffold Protein 7 (MPP7) to BC, despite that there has been no research evaluating the relationship between MPP7 genetic polymorphisms and BC susceptibility. We aimed to investigate the potential association of the MPP7 gene with the susceptibility to BC in Han Chinese individuals. Methods In total, 1390 patients with BC and 2480 controls were enrolled. For genotyping, 20 tag SNPs were chosen. The serum levels of protein MPP7 were measured in all subjects using an enzyme‐linked immunosorbent assay. Genetic association analysis was performed in both genotypic and allelic modes, and the relationship between BC patients' clinical features and genotypes of relevant SNPs was examined. The functional implications of significant markers were also evaluated. Results After adjusting for Bonferroni correction, SNP rs1937810 was found to be significantly associated with the risk of BC (p = 1.19 × 10−4). The odds ratio of CC genotypes in BC patients was 49% higher than in controls (1.49 [1.23–1.81]). Serum MPP7 protein levels were significantly higher in BC patients than in controls (p
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