Objective To investigate the clinical manifestation of patients with Wilson's disease and depressive disorder and the pathogenesis of this disease. Methods Traditional Chinese medicine syndrome typing was performed for 120 patients who were diagnosed with Wilson's disease and depressive disorder. The scores of Hamilton depression rating scale-24 (HDRS-24), self-rating depression scale(SDS), and unified Wilson's disease rating scale (UWDRS) were determined, and the levels of 5-hydroxytryptamine (5-HT), dopamine (DA), interleukin-4(IL-4), interleukin-6(IL-6), and interleukin-10(IL-10) were measured. The scores of the above scales, neurotransmitters, and inflammatory factors were compared between the patients with different syndromes. Results Among the 120 patients with depression, 114 (95.0%) had depressed mood, 52 (43.3%) had reduced interest in work and life, 26 (21.7%) had somatization symptoms, 83 (69.2%) had the sense of decline in ability, and 68 (56.7%) had sense of inferiority; other depressive symptoms were relatively uncommon. The patients with intermingled phlegm and blood stasis had significantly higher HDRS-24, SDS, and UWDRS scores than those with the syndrome of spleen-kidney Yang deficiency or internal retention of damp-heat (P<0.05); the patients with the syndrome of spleen-kidney Yang deficiency had significantly more depressive symptoms than those with the syndrome of internal retention of damp-heat (P<0.05); compared with the patients with spleen-kidney Yang deficiency and internal retention of damp-heat, the patients with intermingled phlegm and blood stasis had significantly lower levels of 5-HT,DA,IL-4, and IL-10 (P<0.05) and a higher level of IL-6 in peripheral blood （P＜0.05）. There were significant differences in the above indices between the patients with the syndrome of spleen-kidney Yang deficiency and those with the syndrome of internal retention of damp-heat (P<0.05). Conclusion The development of depressive symptoms in Wilson's disease may be associated with the changes in the neurotransmitters 5-HT and DA and the inflammatory factors IL-4, IL-6, and IL-10 due to copper deposition in brain, and patients with intermingled phlegm and blood stasis tend to have the most severe depressive symptoms, which may be caused by the fact that phlegm stasis can easily affect the levels of 5-HT,DA, IL-4,IL-6, and IL-10 in the body.