ABSTRACT Objective: To investigate the relationship between the expression of cyclooxygenase-2 (COX-2) and inhibitor of apoptosis proteins (p53, survivin and Bcl-2) in the primary tumor and lymph node metastases (LNMs) of gastric cancer of elderly patients. Methods: The expressions of COX-2, p53, survivin and Bcl-2 in the surgical specimens from 33 elderly patients (≥60 years) with gastric cancer and lymph node metastases were detected by immunohistochemical staining, and the expressions of the above 4 proteins in the primary lesion and involved lymph nodes from 32 patients (<60 years) were determined by the same approach to serve as a control. The expression differences between the two groups and between the primary lesion and metastases were compared, and the correlations among them were also analyzed. Results: Of the elderly patients, the Bcl-2 expression was significantly higher in the metastases than that in the tissues of the primary tumor (P<0.05), no significant differences were noted in the expressions of COX-2, p53 and survivin between primary tumor and metastases (all P>0.05), and there were positive correlations between the primary tumor and metastases in the expressions of p53 and Bcl-2 (r=0.5470 and 0.4969, both P<0.01). In the primary tumor of elderly patients, there were positive correlations between COX-2 and survivin, and between COX-2 and Bcl-2 as well (r=0.5053 and 0.5741, both P<0.01), while a negative correlation was found between survivin and Bcl-2 in metastases of elderly patients (r=–0.5414, P<0.05). The expressions of p53, survivin and Bcl-2 in the primary tumor of elderly patients were significantly higher than those of the control patients (all P<0.05), while only COX-2 expression was higher than that of control group in the metastases. Conclusion: The COX-2 expression in the primary tumor and lymph node metastases of the patients older than 60 years is different from that of the patients below 60 years of age, and this may induce a special apoptosis inhibition pathway that differs from that of patients of other age groups.