Abstract：Objective：To observe the effectiveness and safety of sertraline combined with acupuncture and moxibustion for perimenopausal depression. Methods：A total of 60 cases of patients with perimenopausal depression of kidney deficiency and liver depression type were randomly divided into the treatment group and the control group，30 cases in each group. Both groups were given the oral administration of sertraline，and the treatment group was additionally treated with acupuncture and moxibustion. Both groups were treated for four weeks. At baseline， after four weeks of treatment， and after eight weeks of follow- up respectively， the quality of life and the depression status of participants were evaluated by Hamilton Depression Scale(HAMD) and Menopause-Specific Quality of Life(MENQOL). Results：The scores of vasomotor symptoms， somatic symptoms and psychological symptoms as well as the total scores in the two groups showed a decreasing trend with the passing of treatment time(P＜0.05). After four- week treatment， the scores of vasomotor symptoms and somatic symptoms as well as the total scores in the two groups were decreased when compared with those before treatment(P＜ 0.05)，and the score of psychological symptoms in the treatment group was decreased(P＜0.05)；the scores of psychological symptoms and somatic symptoms as well as the total score in the treatment group were lower than those in the control group (P＜0.05). After eight weeks of follow- up，the scores of vasomotor symptoms and somatic symptoms as well as the total scores in the two groups were decreased when compared with those after four-week treatment(P＜0.05)，and the scores of vasomotor symptoms and psychological symptoms in the treatment group were lower than those in the control group(P＜ 0.05). HAMD scores in the two groups showed a decreasing trend with the passing of treatment time(P＜0.05). After fourweek treatment，HAMD scores in the two groups were decreased when compared with those before treatment(P＜0.05)， but the comparison between the two groups showed no significant difference(P＞0.05). After eight weeks of follow-up，the HAMD score in the treatment group was further decreased when compared with that after four- week treatment(P＜0.05)， and the HAMD score in the control group showed no significant difference when compared with that after four- week treatment(P＞0.05)； the HAMD score in the treatment group was lower than that in the control group(P＜0.05). During treatment， no serious adverse reaction occurred in the two groups. Conclusion： The therapy of sertraline combined with acupuncture and moxibustion for patients with perimenopausal depression can effectively improve their depression state and quality of life.