Abstract：Objective：To observe the clinical effect of Xiaokui Qingyou tang combined with quadruple chemotherapy for helicobacter pylori(Hp) positive peptic ulcer. Methods： A total of 120 cases of patients with HP positive peptic ulcer were selected and divided into the control group and the treatment group according to the random number table method，60 cases in each group. The control group was given quadruple chemotherapy with omeprazole， amoxicillin， clarithromycin and bismuth pectin，and the treatment group was additionally treated with Xiaokui Qingyou tang based on the treatment of the control group. After eight weeks of treatment，the clinical effect and Hp eradication rate in the two groups were evaluated. Before and after treatment， Chinese medicine syndrome scores and gastric mucosal barrier defense function in the two groups were evaluated. During treatment，the adverse reactions were observed and recorded. Results：The total effective rate was 86.67% in the treatment group and 68.33% in the control group，the difference being significant(P＜0.05). The Hp eradication rate was 75.00% in the treatment group and 53.33% in the control group， the difference being significant(P＜ 0.05). Before treatment，there was no significant difference being found in the comparison of Chinese medicine syndrome scores between the two groups(P＞0.05). After treatment， Chinese medicine syndrome scores in the two groups were decreased when compared with those before treatment(P＜0.05)，and the score in the treatment group was lower than that in the control group(P＜0.05). Before treatment， there was no significant difference being found in the comparison of the levels of β-catenin and osteopontin(OPN) in serum between the two groups(P＞0.05). After treatment，the levels of serum indexes of β-catenin and OPN in the two groups were decreased when compared with those before treatment(P＜0.05)， and the above two indexes in the treatment group were lower than those in the control group(P＜0.05). The incidence of adverse reactions was 11.67% in the treatment group and 13.33% in the control group， there being no significant difference between the two groups(P＞0.05). Conclusion：The application of self-made Xiaokui Qingyou tang combined with quadruple chemotherapy for patients with Hp positive peptic ulcer is safe and effective， which can improve clinical symptoms， clinical effect and Hp eradication rate， effectively regulate the levels of β- catenin and OPN， and protect the damaged gastrointestinal mucosa.