In order to investigate the prognostic significance of P53 protein expression in the patients with colorectal adenocarcinoma, we used the P53 monoclonal antibody and ABC immunohistochemical method combined with the repairing method for antigen by microwave oven to study the relationship between the overexpression of P53 protein and the prognosis in 40 cases of colorectal adenocarcinoma. The results showed that 65% (26/40) cases of colorectal adenocarcinoma were positive for overexpression of P53 protein. The 5-year survival rate for positive cases was 50%, but 87.5% for negative cases. These findings suggest that the overexpression of P53 protein closely associates with the prognosis in colorectal adenocarcinoma (P < 0.05), thus it might become a new prognostic indicator. The prognosis in colorectal adenocarcinoma could be predicted thoroughly by considering the expression of P53 protein in combination with the traditional prognostic factors.