Abstract： Objective： To observe the clinical effect of Chaihu and Longgu Muli Decoction combined with Paroxetine Hydrochloride Tablets on depression. Methods： A total of 84 cases of patients with depression were included in the study， and were divided into the treatment group and the control group according to the random number table method，with 42 cases in each group. The control group was treated with Paroxetine Hydrochloride Tablets，and the treatment group was treated with Chaihu and Longgu Muli Decoction combined with Paroxetine Hydrochloride Tablets. After 8 weeks of treatment， the clinical effects， traditional Chinese medicine (TCM) syndrome scores， Hamilton Depression Scale (HAMD) scores，Pittsburgh Sleep Quality Index (PSQI) scores，and the levels of brain-derived neurotrophic factors (BDNF) and 5- hydroxytryptin (5- HT) in serum in the two groups were evaluated. Results： The total effective rate was 95.24% in the treatment group and 80.95% in the control group，the difference being significant (P＜0.05). After treatment， TCM syndrome scores in the two groups were decreased when compared with those before treatment (P＜0.05)， and the TCM syndrome score in the treatment group was lower than that in the control group (P＜0.05). After treatment，the scores of HAMD and PSQI in the two groups were decreased when compared with those before treatment (P＜0.05)， and the scores of HAMD and PSQI in the treatment group were lower than those in the control group (P＜0.05). After treatment， the levels of BDNF and 5- HT in the two groups were increased when compared with those before treatment (P＜0.05)， and the levels of BDNF and 5- HT in the treatment group were higher than those in the control group (P＜0.05). Conclusion： Chaihu and Longgu Muli Decoction combined with Paroxetine Hydrochloride Tablets has a definite curative effect on depression， which can significantly relieve clinical symptoms，improve depression degree and sleep quality，and can effectively regulate the levels of neurological factors and neurotransmitters.