To observe the clinical efficacy of acupuncture at back-shu and front-mu acupoints in the treatment of depression patients with liver depression and spleen deficiency syndrome.Methods:A total of 100 patients diagnosed with depression with liver depression and spleen deficiency syndrome treated at the Second Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine from January 2022 to December 2022 were enrolled and randomly divided into control group and observation group，with 50 cases in each group.The control group was treated with oral administration of escitalopram for one month，while the observation group were treated with acupuncture at back-shu and front-mu acupoints based on the control group，with treatment administered once every 2 days for a total of 15 times.The main symptoms，depression severity，quality of life scores，serum 5-hydroxytryptamine(5-HT) levels，intestinal flora，adverse reactions，recurrence rate，and clinical efficacy were compared before and after treatment between the two groups.Results:After treatment，the observation group had higher scores in the Short Form Health Survey(SF-36)，serum 5-HT levels，and quantities of Lactobacillus and Bifidobacterium in fecal specimens than the control group(all P<0.05)，while the scores of main symptoms，Hamilton Depression Rating Scale(HAMD-24)，and quantities of Escherichia coli and Enterococcus in fecal specimens were lower than those in the control group(all P<0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P>0.05).The recurrence rate in the observation group at 6 months after treatment was slightly lower than that in the control group，but the difference was not statistically significant(P>0.05).The total effective rate in the observation group after treatment was higher than that in the control group(P<0.05).Conclusion:Acupuncture at back-shu and front-mu acupoints has definite efficacy in the treatment of depression patients with liver depression and spleen deficiency syndrome，effectively improving symptoms，reducing depression severity，enhancing quality of life，regulating serum 5-HT levels，and improving intestinal flora distribution，with high safety.