Abstract: Objective To study efficacy of Sertraline hydrochloride tablets in the treatment of peptic ulcer and depression in patients with Helicobacter pylori infection. Methods Total 166 cases of Hp-positive peptic ulcer patients with depression were randomly divided into treatment group(86 cases) and control group(80 cases).The two groups were given the same triple therapy to treat Hp positive peptic ulcer,thetreatment group was given sertraline to treat thedepression,and the control group was given amitriptyline to treatdepression.The degree of pain,results of the electronic gastroscopy,Hp clearance rate,HAMD score and adverse drug reactions were observed. Results Total 166 Hp strains(75.9%) were highly resistant to metronidazole,but lowresistant to amoxicillin,levofloxacin,furazolidone andclarithromycin.After8 weeks oftreatment,abdominal pain was improved significantly in both groups,andthe treatment group was better than the control group,the difference was statistically significant(P<0.05).HAMD score for the two groups was (12.4±3.6) and (19.0±3.9),respectively,significantly decreased after thetreatment,and the HAMD score in the treatment group was lower than that in the control group,the difference was statistically significant (P<0.05).The efficiency of the treatment group was 55.8%,the total efficiency was 89.5%,the markedly effective rate and total effective rate in the treatment group was significantly higher(χ²=10.597,6.019,all P<0.05) as compared with the control group.Hp clearance rate in treatment group was 93.0%(80/86) and in the control group was 78.8%(63/80),the difference was statistically significant(P<0.05).The incidence of adverse reactions was no statistically significant(χ²=1.457,P>0.05). Conclusion Sertraline hydrochloride tablets combined with triple therapy can effectivelytreat the depression in Hp positive peptic ulcerpatients,with fewer adverse reactions and a high clinical value.