Objective?To analyze the characteristics of gastric ulcer disease and evaluate the efficacy of esomeprazole and omeprazole in the treatment of gastric ulcer disease, so as to provide clinical reference. Methods?80 patients with gastric ulcer treated in Jianxin Hospital of Fujian province from January 2018 to January 2021 were selected for retrospective analysis, and were randomly divided into routine group and study group, with 40 patients in each group. Patients in the routine group were treated with omeprazole and patients in the study group were treated with esomeprazole. The therapeutic effects and adverse reactions of the two groups were compared; The epidermal growth factor (EGF) and tumor necrosis factor- α（TNF- α）、interleukin-6 (IL-6) level after treatment were analyzed. The hospitalization time and the disappearance time of clinical symptoms were analyzed and compared between the two groups. Results?The treatment effective rate of patients in the study group was 97.50%, which was significantly higher than 75.00% in the routine group (P ＜ 0.05). The probability of adverse reactions in the study group was 2.50%, which was significantly lower than that in the routine group. The probability of adverse reactions in the study group was significantly lower than that in the routine group (P ＜0.05). The increase of EGF in the study group was significantly higher than that in the routine group, while TNF- α、IL-6 was significantly lower than that in routine group (P ＜0.05). The hospitalization time and the disappearance time of clinical symptoms in the study group were significantly shorter than those in the routine group (P ＜0.05). Conclusion?The effect of esomeprazole in the treatment of gastric ulcer is more obvious than that of omeprazole. It can not only significantly improve the clinical symptoms of patients, alleviate them and recover them as soon as possible, but also reduce the probability of adverse reactions. It is worthy of wide application in clinic.