Objective: To evaluate the effects of the method of transporting spleen and resolving dampness based on the syndrome differentiation of liver depression and spleen deficiency combined with traditional Chinese medicine emotional regulation on symptoms, sleep and quality of life in patients with cancer-related depression (CRD). Methods: A total of 108 patients with CRD were selected as the research subjects and divided into two groups according to the treatment methods. 54 patients in the control group were given the treatment of regulating emotions with traditional Chinese medicine five-element music, while 54 patients in the study group were treated with the method of transporting the spleen and eliminating turbidity based on the differentiation and treatment of liver depression and spleen deficiency syndrome on the basis of the treatment in the control group. Both groups were treated for 8 weeks. The depressive symptoms [Hamilton Depression Rating Scale (HAMD) score and reduction rate, remission rate, and effective rate], sleep status (falling asleep time, sleep time, sleep efficiency, sleep disorders, daytime function, hypnotic drugs, and sleep quality), and quality of life (EORTC QLQ-C30 score) before and after treatment were compared between the two groups. Results: The HAMD score of the study group was lower than that of the control group after 8 weeks of treatment. The score reduction rate, remission rate and effective rate were higher than those of the control group (P<0.05). The sleep onset time, sleep duration, sleep efficiency, sleep disorders, daytime function, hypnotic drugs, sleep quality score and the difference were all lower than those of the control group (P<0.05). The scores of physical function, role function, cognitive function, emotional function and social function in EORTC QLQ-C30 were higher than those of the control group (P<0.05). Conclusion: The method of transporting spleen and resolving dampness based on the syndrome differentiation of liver depression and spleen deficiency combined with traditional Chinese medicine emotional regulation can improve the symptoms and sleep quality of CRD patients and improve their quality of life.