The p53 protein is closely involved in the carcinogenesis of many kinds of cancers. Though the prognostic role of p53 expression for the survival of colorectal cancer (CRC) patients has been preliminarily identified, the prognostic effect of p53 expression in patients with completely resected CRC is still unclear. Therefore, a retrospective cohort study was performed to assess the prognostic role of p53 expression for overall survival in patients with completely resected CRC. A total of 153 patients (mean age 50.9 years) with completely resected CRC was finally included in the retrospective cohort study. Kaplan-Meier product-limit methods and log-rank test were used to estimate overall survival distribution and test the difference. In addition, multivariable analysis by Cox regression model was also used to test the prognostic role of p53 expression on overall survival by adjusting for other confounding factors. Of those 153 CRC patients, 62 (40.5 %) were positive for p53 protein expression in the tumor tissues. The log-rank test showed that there was an obvious difference in the overall survival between the p53-positive group and the p53-negative group (P < 0.001). Multivariable analysis by Cox regression model further showed that p53 protein expression was an independent predictor of shorter overall survival in patients with completely resected CRC (hazard ratio [HR] = 1.77; 95 % confidence interval [95 % CI] 1.15-2.71, P = 0.009). Therefore, p53 protein expression in the tumor tissue is an independent predictor of shorter overall survival in patients with completely resected CRC.