Abstract: Objective: To investigate the correlation between high risk HPV16 and HPV 18 infection and disorderof p53, MCM7 protein expression in breast cancer and benign breast diseases; and to explore the mechanisms involved inthe carcinogenesis and progression of breast cancer. Methods: We employed SP immunohistochemistry to detect the ex-pression of HPV16, 18E6, p53 and MCM7 in 55 cases of breast cancer, 5 cases of ductal carcinoma in situ and its cor-responding adjacent breast tissues, 30 cases of breast adenosis and 30 cases of normal breast tissues. Results: The ex-pression of HPV16, 18E6, p53 and MCM7 in the 55 cases of breast cancer were 58.18%, 38.18% and 96.36%, respec-tively, higher than those in normal breast tissues and breast adenosis (P<0.01, P<0.001, P<0.05). The expression of p53in groups with expression of HPV16 and 18E6 was lower than that in groups without HPV16 and 18E6 expression (P<0.001). The expression of HPV16 and 18E6 was negatively correlated with the expression of p53 (r=0.5769, P<0.001),but positively correlated with the expression of MCM7 (r=0.5442, P<0.001). In the group of invasive ductal carcinoma, theexpression MCM7 protein was associated with histological grading, axillary lymph node metastasis, and tumor size (P<0.01,P<0.03, P<0.01). Conclusion: High risk HPV16 and HPV 18 infection causes inactivation of p53 protein and high ex-pression of MCM7 protein, leading to disorder of cell cycle replication regulation, which may play an important role in thepathogenesis and progression of breast cancer. The high expression of MCM7 was associated with cell proliferation, inva-siveness and metastasis of invasive ductal carcinoma. The combined detection of HPV16, 18E6 and MCM7 protein is help-ful for evaluation of the epithelial proliferation and early diagnosis. It can also serve as a useful predictor for biological be-haviors and prognosis of breast cancer.