Abstract: To study the expression of MAD2 and p16 gene in colorectal cancer and to demonstrate the relation between the expression of MAD2 and p16 in colorectal cancer，adenoma and normal tissue and to evaluate their clinical significances. Methods Immunohistochemistry method and real-time fluorescence quantitative PCR were used to analyze the expression of MAD2 in the colorectal cancer，adenoma and normal tissue. PCR amplification and DNA sequencing were performed to detect the mutations of MAD2. p16 was determined in the colorectal cancer and normal tissue by immunohistochemistry methods. Results The expression of MAD2 in colorectal cancer were obviously higher than that in adenoma and normal tissue（66.7％vs. 39.6％vs. 22.9％）. There were obvious difference among colorectal cancers，adenoma and normal tissue （P＜0.001），and it were related to tumor differentiation and survival time （P＜0.05）. No mutation of MAD2 gene was found in colorectal cancer. The rate of p16 positive expression in colorectal cancer and normal mucosa was 47.9%and 16.7%，respectively. There was significant difference between normal mucosa tissue and colorectal cancers（P＜0.001）. Conclusion Our data indicates that positive expression of MAD2 and p16 was mainly involved in colorectal carcinogenesis and MAD2 was associated with prognosis of colorectal cancer.