Abstract： Objective： To observe the clinical effect of modified Guipi Decoction for cancer- related fatigue (CRF) with spleen qi deficiency syndrome，and its effect on the levels of hemoglobin (Hb)，albumin (Alb)， CD4 + CD25hiCD127low， and CD4 + cells absolute count in patients. Methods： A total of 60 cases of CRF patients with spleen qi deficiency syndrome were selected and divided into the control group and the treatment group according to the random number table method，with 30 cases in each group. The control group received interventions such as music relaxation therapy and psychological counseling， and the treatment group was treated with modified Guipi Decoction based on the treatment of the control group. Both groups were treated for 2 weeks. The scores of Chinese version of the Brief Fatigue Inventory (BFI-C)， traditional Chinese medicine (TCM) symptoms， Pittsburgh Sleep Quality Index (PSQI)， and Karnofsky (KPS)， as well as the levels of Hb， Alb， CD4 + CD25hiCD127low， and CD4 + cells absolute count were compared before and after treatment between the two groups. The adverse reactions were recorded in the two groups. Results： After treatment， the scores of present fatigue， fatigue in the past 24 hours， maximum fatigue in the past 24 hours， and influence of emotions， work， life enjoyment， general activities， walking abilities and interpersonal relationships in the two groups were decreased when compared with those before treatment (P＜0.05)； the BFI- C scores of the above nine items in the treatment group were lower than those in the control group (P＜0.05). The scores of reduced diet， discomfort in the stomach after eating， fatigue and lack of strength， loose and thin stools， and yellow complexion in the two groups were decreased when compared with those before treatment (P＜0.05)；the scores of the above five TCM symptoms in the treatment group were lower than those in the control group (P＜0.05). The PSQI scores in the two groups were decreased when compared with those before treatment (P＜0.05)，and the PSQI score in the treatment group was lower than that in the control group (P＜0.05). The KPS scores in the two groups were increased when compared with those before treatment (P＜0.05)， and the KPS score in the treatment group was higher than that in the control group (P＜0.05). The levels of Hb and Alb in the treatment group were increased when compared with those before treatment and were higher than those in the control group (P＜0.05). There was no significant difference being found in Hb and Alb levels between the control group before and after treatment (P＞0.05). The CD4+CD25hiCD127low level in the treatment group was decreased when compared with that before treatment and was lower than that in the control group (P＜0.05). The level of CD4 + cells absolute count in the treatment group was increased when compared with that before treatment and was higher than that in the control group (P＜0.05). There was no significant difference in levels of CD4+CD25hiCD127low and CD4+ cells absolute count before and after treatment in the control group (P＞0.05). During the treatment period， neither group experienced any significant adverse reactions. Conclusion： Modified Guipi Decoction can effectively improve the clinical symptoms and nutritional status of CRF patients with spleen qi deficiency syndrome，improve their sleep and quality of life，and improve the immune function.