PURPOSE: In spite of curative surgery and early postoperative intraperitoneal chemotherapy, the prognosis of patients with gastric cancer involving the serosal surface is poor. The aim of this study was to analyze p53 protein overexpression in these patients and to clarify the usefulness of p53 mutation as a prognostic indicator. METHODS: p53 protein overexpression was assessed by immunohistochemistry in 123 gastric cancer specimens. The correlation between p53 protein overexpression and clinicopathologic parameters and prognosis of the patients were analyzed. RESULTS: Overexpression of p53 protein was identified in 67 (54.5%) tumors and was more frequent in differentiated tumors than in undifferentiated tumors (67.4% vs. 46.8%; P=0.026). However, there were no statistically significant differences in the frequency of p53 protein overexpression according to age, sex, depth of invasion, lymph node metastasis, distant metastasis, pathologic stage, and Lauren classification. There was no statistically significant difference in 5-year survival rate according to the p53 protein overexpression (P=0.565). CONCLUSION: Overexpression of p53 protein could not predict the effectiveness of early postoperative intraperitoneal chemotherapy. Therefore, it could not be used as a prognostic indicator in patients with advanced gastric cancer who underwent gastrectomy and early postoperative intraperitoneal chemotherapy.