Abstract: OBJECTIVE To investigate the relationship between Human papillomavirus (HPV) infection and the breast cancer gene expression of C-erbB-2, fully aware of the correlation between HPV and breast cancer, so as to provide reference of improving the prevention and treatment of breast cancer medical standards. METHODS A total of 168 cases of breast disease patients treated in the hospital from Feb. 2014 to Feb. 2015 were selected as research subjects and grouped according to the patient's disease condition, including 84 cases of breast cancer patients as cancer group, 84 cases of patients with hyperplasia of mammary glands as hyperplasia group, and 84 samples of normal breast tissue taking nearby hyperplasia lesions in 84 patients as control group, the C-erbB-2 and positive rates of HPV in three groups were compared. SPSS 19.0 was used for statistic analysis. RESULTS The positive rates of C-erbB-2 and HPV in cancer group were 73.81% and 41.67%, which were higher than the other two groups obviously (P＜0.05). The patients in stage Ⅳ had positive expression of C-erbB 100.00%, and the positive rate of HPV-16RNA was 80.00%, HPV-18DNA positive expression rate 80.00%. As the disease worsens, C-erbB-2 and expression of HPV increased alone with it. CONCLUSION The expression of C-erbB-2 gene has great relationship with HPV infection. If the expressing of C-erbB-2 gene is high, there is the risk of HPV infection.