To investigate the safety of Xuhanting Granules combined with selective serotonin reuptake inhibitor(SSRI) and the effect on health-related quality of life in patients with depression by comparing with SSRI alone.Methods:Ninety-five patients with acute depressive disorder treated in the Third Affiliated Hospital of Sun Yat-sen University from January 2017 to December 2019 were enrolled and randomly divided into an observation group(n=46) and a control group(n=49) according to the random number table method.The patients in the control group were treated with SSRI alone，and those in the observation group were treated with Xuhanting Granules combined with SSRI.Both groups were treated for eight weeks.Regular visits were carried out and the scores of the Self-Rating Depression Scale(SDS)，36-Item Short Form Survey(SF-36)，Columbia Suicide Severity Rating Scale(C-SSRS)，Barnes Akathisia Scale(BAS)，and Abnormal Involuntary Movement Scale(AIMS) were measured.Results:After eight weeks of treatment，the SDS score of the observation group was lower than that of the control group(P<0.01)，but the SF-36 score had no significant difference.In terms of safety，there was no significant difference in C-SSRS score between the two groups，while BAS and AIMS scores in the observation group were significantly lower than those in the control group(P<0.01).Conclusion:Xuhanting Granules combined with SSRI in the treatment of depression can effectively improve the social function of patients with depression and reduce extrapyramidal side effects with good safety.