Objective To explore the mutation frequency of single nucleotide polymorphism (SNP) in the breast cancer susceptibility gene (BRCA)1/2 coding region and its relationship with clinicopathological features of Chinese patients with hereditarily high-risk breast cancer. Methods We extracted the DNA of peripheral blood mononuclear cells from 69 Chinese hereditarily high-risk patients with breast cancer, and detected the sequences of 49 exons in BRCA1/2 coding region by second-generation sequencing technology. At the same time, we collected the clinicopathological data of all patients, including the age at diagnosis, the age at menarche, first pregnancy age, TNM stage, immunohistochemical status, whether it was bilateral breast cancer and/or with family history, and analyzed the relationship of site polymorphism of BRCA1/2 coding region with clinicopathological features of breast cancer. Results A total of 34 SNPs were identified, among which 14 were located in the BRCA1 and 20 in the BRCA2 coding region, including 18 high frequency sites and 16 low frequency sites. The rs80356892 site polymorphism of BRCA1 coding region was significantly correlated with the clinicopathological features of breast cancer. The patients with rs80356892 site mutation were inclined to have bilateral breast cancer (P=0.005), family history (P=0.029) and triple negative breast cancer (P<0.001). In addition, SNP in rs80356892 site was negatively correlated with the expressions of estrogen receptor and progesterone receptor. Conclusion SNP in BRCA1/2 coding region are associated with the onset risk and the clinicopathological features of breast cancer. The detection of SNP may contribute to risk assessment of breast cancer and screening and prevention of hereditary breast cancer.