Abstract：Objective：To observe the clinical effect of Shugan Jieyu capsules combined with fluoxetine for depression and its effect on heart rate variability. Methods： A total of 108 cases of patients with depression were selected as the study objects and divided into two groups according to the random number table method，54 cases in each group. The control group was treated with fluoxetine hydrochloride capsules，and the study group was additionally treated with Shugan Jieyu capsules based on the treatment of the control group. The Hamilton Depression Scale(HAMD)， Hamilton Anxiety Scale(HAMA)， Pittsburgh Sleep Quality Index(PSQI)，the HRV indexes including standard deviation of the normal- to- normal sinus nodeinitiated R-R intervals(SDNN)，Low Frequency(LF) and high frequency(HF)，the clinical effect，and the incidence of adverse reactions in the two groups were compared. Results：After six-week treatment，the HAMD and PSQI in the two group were significantly lower than those before treatment，and the above indexes in the study group were all lower than those in the control group， differences being significant(P＜0.05)； HAMA in the two groups were lower than those before treatment， differences being significant(P＜0.05)， but there was no significant difference being found in the comparison of HAMA between the two groups(P＞0.05). After six- week treatment， the levels of SDNN and HF in the study group were significantly higher than those before treatment， and those in the control group， the level of LF in the study group was significantly lower than those before treatment，and those in the control group，differences being significant(P＜0.05). The total effective rate of clinical effect was 94.44% in the study group， significantly higher than that of 81.48% in the control group， the difference being significant(P＜0.05). There was no significant difference being found in the comparison of incidence of adverse reactions between the two groups(P＞0.05). Conclusion： The treatment of fluoxetine combined with Shugan Jieyu capsules can significantly decrease depression degree and improve sleep quality and HRV without increasing adverse reactions.