Objective To observe the action and correlation of p16 and estrogen receptor (ER) in papillary thyroid cancer (PTC).Methods Using immunohistochemical method, the p16 and ER in 50 cases of PTC were detected. Results The expression of p16 and ER was associated with the cellular differentiation, the lymphatic metastasis and prognosis in PTC. Conclusion It is helpful to detect the p16 protein and ER for analyzing the cellular differentiation degree and prognosis in PTC.