The clinical importance of biologic markers remains elusive in gastric cancer. The aim of this study was to evaluate the prognostic value of p53, Ki-67, and COX-2 in gastric cancer. This retrospective study examined based on medical records of postoperative immunohistochemical test of 176 patients who demonstrated high expression of all three biological markers being tested (p53, Ki-67, and COX-2), among 357 gastric cancer patients who underwent surgical resection consecutively. This study demonstrates the correlation with biologic marker between clinical relationship and recurrence free survival (RFS). A positive correlation was observed between the expression of Ki-67 and p53, and a positive correlation was also observed between the expression of Ki-67 and COX-2 Expression of p53 did not correlate with any of the clinicopathological variables examined. Both Ki-67 and COX-2 expression significantly correlated with tumor depth, classified as early gastric cancer and advanced gastric cancer. The expression of COX-2 significantly correlated with tumor differentiation, with more tumors being of the undifferentiated type than of the differentiated type in the COX-2 positive group. A significant difference between p53 and RFS, also COX-2 expression and RFS was observed. This study showed that only p53 and COX-2 have significantly correlated with the RFS of gastric cancer.