Abstract： Objective： To observe the clinical effect of the therapy of Baihe Dihuang tang combined with voltioxetine hydrobromide on depression and its effect on stress response. Methods：A total of 84 patients with depression were selected and divided into the control group and the study group according to the random number table method，with 42 cases in each group. The control group was treated with voltioxetine hydrobromide， and the study group was treated with voltioxetine hydrobromide combined with Baihe Dihuang tang. Both groups were treated for two courses，two months being a course. The clinical effect，and the changes in the scores of Hamilton Depression Scale(HAMD) and levels of related stress response indexes， including serum cortisol(CORT)， malondialdehyde(MDA) and superoxide dismutase(SOD) before and after treatment were observed and compared between the two groups. Results：The total effective rate was 95.2% in the study group and 81.0% in the control group，the difference being significant(P＜0.05). After 1，2 courses of treatment，the HAMD scores in both groups were decreased when compared with those before treatment(P＜0.05)，and the HAMD score in the study group was lower than that in the control group at the same time point(P＜0.05). After 2 courses of treatment，the levels of CORT and MDA in both groups were decreased when compared with those before treatment(P＜0.05)，and the levels of SOD in both groups were increased(P＜0.05). The levels of CORT and MDA in the study group were lower than those in the control group(P＜0.05)， and the SOD level was higher than that in the control group(P＜0.05). Conclusion： The combined treatment of voltioxetine hydrobromide and Baihe Dihuang tang can significantly improve the clinical symptoms of patients with depression，enhance the total effective rate of treatment and relieve stress response.