Objective To explore the clinical effect of Chaishao Yuhuan Decoction combined with Kaiyu acupuncture in the treatment of menopausal depression. Methods A total of 150 patients with menopausal depression in our hospital from April 2020 to July 2021 were selected and divided into 3 groups according to random number table method，with 50 cases in each group. The control group was treated with flupentixol and melitracen. Observation group 1 was treated with Kaiyu acupuncture while taking flupentixol and melitracen. Observation group 2 was treated with Chaishao Yuhuan Decoction combined with Kaiyu acupuncture. All 3 groups were treated for 8 weeks. The treatment effect and the incidence of adverse reactions in the 3 groups were observed. Hamilton Self⁃ rating Anxiety Scale（HAMA），Hamilton Self ⁃ rating Depression Scale（HAMD），Menopause Clinical Symptom Survey（Kupperman），and Pittsburgh Sleep Quality Index（PSQI）were used to assess the treatment effect and serum Luteinizing Hormone（LH），Follicle Stimulating Hormone（FSH），Estradiol（E2），miR ⁃155 and miR ⁃ 146a levels were compared among the three groups. Results The total effective rate in the observation groups was higher than that in the control group（P < 0.05）. After 8 weeks of treatment，the score of each scale，LH，FSH， miR⁃155 and miR⁃146a in observation group 2 were lower than those in observation group 1 and control group，but E2 was higher. At the same time，the improvement of the above indexes in observation group 1 were better than those in the control group（P < 0.05）. There was no statistically significant difference in the incidence of adverse effects among the three groups（P > 0.05）. Conclusion Chaishao Yuhuan Decoction combined with Kaiyu acu⁃ puncture is safe and effective for relieving the symptoms of menopausal depression，and regulating the expression of miR⁃155 and miR⁃146a.