Objective To investigate expression of p16 protein in breast cancer and its clinical significance. Methods Using immunohistochemical techniques (LSAB) the expression of p16 protein in 107 breast carcinomas was examined. Results The positive rate of p16 protein expression was 40.19% (43/107). The p16 protein over expression of the cases surviving ≤5 years and surviving ≥10 years were 8.00% and 75.68% respectively. Conclusion Expression of p16 protein might play an important role in the prognosis of breast cancer.