Objective To study the correlation between the expression of p16 protein and TCM syndrome differentiation type of III-IV phase and rectal cancer. Methods The expression of p16 in normal tissues and III-IV in colorectal carcinoma was detected by immunohistochemical staining， differentiation and typing of III-IV phase and rectal carcinoma， the correlation between TCM syndrome types and the expression of p16 was analyzed. Results 1. The expression level of p16 in the normal control group was significantly higher than that in the III-IV phase and colorectal carcinoma tissues， the difference was statistically significant（P<0.05）， and with the progress of pathological staging， the difference was significantly increased. 2. Correlation between TCM syndrome differentiation type of III-IV and p16 protein expression in colorectal cancer， the difference was statistically significant（P<0.05）. Conclusion 1. The loss of p16 protein expression is related to the occurrence and development of colorectal cancer， the loss of p16 protein expression can be used as an index to evaluate the biological behavior and prognosis of colorectal cancer. 2. p16 protein expression in different TCM syndrome types of III-IV stage， there are some differences in colorectal cancer.