Breast cancer is the most common type of cancer among women worldwide, and the incidence of breast cancer is increasing in the developing world. Estrogen exposure is a major risk factor for breast cancer, and estrogen oxidative metabolites have been implicated in chemical carcinogenesis. Xeroderma pigmentosum complementary group C (XPC) plays an important and multifaceted role in cell protection from oxidative DNA damage. Thus, XPC inactivation may be involved in the early stage of breast cancer. The aim of this study was to investigate the expression of XPC protein in sporadic breast cancer tissues and determine whether XPC expression influences breast cancer malignancy and clinical outcome. Fifteen cases of adjacent non-tumor breast tissue, 28 cases of fibroadenomas and 235 cases of breast carcinomas were examined by immunohistochemistry using polyclonal antibody to XPC. Both cytoplasmic and nuclear expression level of XPC were downregulated in breast carcinoma when compared to non-tumor tissues (P < 0.05). The nuclear expression level of XPC was significantly associated with expression of BCL2 (r = 0.231, P = 0.033) and p53 (r = 0.205, P = 0.011), and nuclear expression of XPC was significantly associated with patients' age (P = 0.024). Neither cytoplasmic nor nuclear expression level of XPC had impact on patients' survival in the whole samples. However, XPC expression was correlated with adverse survival in HER2-positive, but not HER2-negative, tumors, as demonstrated by Kaplan-Meier analysis. Our results suggested that the XPC protein is involved in the occurrence and progression of breast cancer.