Abstract: Approaching the risk factor of P53 protein overexpression to provide a molecular basis for the etiology of colorectal cancer(CRC).The tumor tissues of 121 CRC surgical patients were detected by SP immunohistochemistry.The correspond patients were divided into p53 overexpression positive group and negative group.Apply the case-case study and SAS software to factor analysis.The P53 overexpression positive rate was 59.50%(72/121);There are five factors associated with P53 overexpression by univariate analysis,they are smoking(OR=2.095),toxic contacting(OR=2.180),smoking of family member(OR=3.09),self-depression(OR=2.300)and vinegar eating(OR=0.800);Moreover,smoking of family member and vinegar eating factors were introduced to multiple non condition logistic regression analysis model(a=0.05),the OR were 3.476 and 0.774 respectively;The special risk factor was smoking for male and smoking of family member for female by sex-stratification multiple analysis.The results showed that the P53 overexpression is related to the smoking and vinegar.