Objective To explore the effect of esomeprazole quadruple therapy on patients with peptic ulcer Helicobacter pylori (Hp) infection. Methods The clinical data of patients with peptic ulcer Hp infection who were treated in our hospital from January 2018 to January 2019 were retrospectively analyzed. A total of 40 patients who received omeprazole quadruple therapy (omeprazole, bismuth potassium citrate, amoxicillin clavulanate tablets, moxifloxacin tablets) were selected as the control group, and a total of 40 patients treated with esomeprazole quadruple therapy (esomeprazole, bismuth potassium citrate, amoxicillin clavulanate tablets, moxifloxacin tablets) were selected to form the observation group. Tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8) and the occurrence of adverse reactions were compared. Results TNF-α, IL-6, IL-8 The level of the observation group was statistically lower than that of the control group (P<0.05); The observation group had a higher Hp negative rate than that of the control group after treatment, and the difference was statistically significant (P<0.05); The incidence of adverse reactions between the two groups was not statistically significant (P>0.05). Conclusion Esomeprazole quadruple therapy can reduce the level of inflammatory index in patients with peptic ulcer Hp infection, promote Hp to negative, and it has fewer adverse reactions and higher safety.