Abstract: Objective To observe the clinical curative effect and safety of traditional Chinese medicine Shugan Hewei decoction on tumor-associated depression with liver-stomach disharmony. Methods This study used a randomized controlled design. Totally 92 patients with tumor-associated depression admitted to our hospital from December 2014 to December 2015 were randomly divided into treatment group(n=46) and control group(n=46). The patients had completed general anti-cancer therapy. The traditional Chinese medicine Shugan Hewei decoction was given to the patients in the treatment group and fluoxetine hydrochloride dispersible tablets was given to those in the control group for 6 weeks. After treatment, the HAMD(Hamilton Depression Scale) score reduction and the change of serum brain-derived neuro-trophic factor(BNDF) levels were observed and compared, and liverstomach disharmony syndromes were also assessed. Results There was no significant difference in gender(male, 28 vs 30), age (41.1±9.78) years vs(44.7±9.65) years, course of disease (9.27±4.12) months vs(7.98±5.66) months between two groups(P> 0.05). At the same time, there was no significant difference in HAMD score (22.10±4.71) vs(21.86±5.6), the serum BNDF levels (19.18±3.25) pg/ml vs(18.63±3.99) pg/ml and the syndrome score (16.53±4.33) vs(15.19±3.17) before treatment in two groups(P> 0.05). After treatment, HAMD score and syndrom score in treatment group were less than those in control group (10.16±5.13) vs(14.12±4.97), P=0.03;(8.98±5.37) vs(13.21±4.65), P=0.08. The HAMD score decreased by 65.2% in the treatment group, and 47.8% in the control group(P=0.094). The serum BNDF levels was(30.16±4.92) pg/ml in the treatment group, and(23.64±3.78) pg/ml in the control group; the total effective rate calculated by syndrome score reduction was 95.7% in the treatment group, and 56.5% in the control group(P< 0.05, respectively). No severe adverse events occurred.Conclusion Traditional Chinese medicine Shugan Hewei decoction can treat tumor-associated depression with liver-stomach disharmony effectively and safely, relieve clinical symptoms and increase serum BDNF level of patients.