Objective To measure the expression of hypoxia inducible factor-1-alpha (HIF-1α) and hypoxia inducible factor-2-alpha (HIF-2α) in the elderly patients with gastric cancer and to analyze its clinical significance. Methods A total of 100 elderly patients with identified gastric cancer treated in the Yangluo Branch from February 2017 to March 2018 were enrolled as the study subjects, and another 100 healthy old individuals (over 65 years old) who received gastroscopy in our branch during the same period were recruited as the control group. The expression of HIF-1α and HIF-2α was detected in the 2 groups. SPSS statistics 17.0 was used to perform the statistical analysis. Student′s t test or Chi-square test was applied for comparison between groups in difference data types. Multivariate logistic regression analysis was employed to screen the independent influencing factors for the expression of the 2 proteins in the patients. Results The positive expression rates of HIF-1α (85.0% vs 8.0%) and HIF-2α (82.0% vs 5.0%) in gastric cancer group were significantly higher than those in control group (P<0.001). Multivariate logistic regression analysis indicated that lymph node metastasis (HIF-1α:OR=5.132,5%CI 1.872-14.325, P=0.008; HIF-2α:OR=4.629, 95%CI 1.754-16.392; P=0.002) and clinical stage (HIF-1α:OR=3.957,5%CI 1.694-8.363, P=0.012; HIF-2α:OR=4.341,5%CI 2.312-10.052, P=0.010) were independent risk factors for the positive expression of HIF-1α and HIF-2α in gastric cancer patients. Conclusion The elderly patients with gastric cancer have higher positive expression rate of HIF-1α and HIF-2α, which may be related with clinical stage and lymph node metastasis.