Objective To observe the nursing effect of acupoint sticking with Xiaoyao San on the fatigue of chronic hepatitis B patients with liver depression and spleen deficiency, and to explore the effect of acupoint sticking with Xiaoyao San on the quality of life of chronic hepatitis B patients. Provide effective traditional Chinese medicine nursing technical services, and promote the application in clinical practice, to explore the development of integrated traditional Chinese and Western medicine nursing. Methods A total of 112 patients with chronic hepatitis B fatigue with liver stagnation and spleen deficiency who were admitted to the liver disease department of a tertiary A-level hospital in Kunming from July 2021 to July 2022 were selected. They were randomly divided into experimental group and control group, 56 cases in each. The control group was given basic treatment and nursing of chronic hepatitis B, and the experimental group was given acupoint sticking nursing technique on the basis of the control group. Both groups were treated for 2 weeks. Observation and comparison of Piper fatigue score and curative effect, quality of life score, TCM syndrome score, interleukin-6 (interleukin-6, hereinafter referred to as IL-6) in serum before intervention, 7 days and 14 days after intervention between the two groups were observed and compared. Concentration changes were evaluated to evaluate the differences in acupoint sticking with Xiaoyao San nursing technology on patients' fatigue symptoms and quality of life improvement. Results Compared with the control group, the Piper fatigue score, TCM symptom score and IL-6 concentration in the experimental group were decreased on the 14th day after the intervention, and the quality of life score was improved, and the difference was statistically significant (P＜0.05). In terms of fatigue curative effect，the difference between the experimental group and the control group was statistically significant (P＜0.05) on the 14th day. Conclusion The application of acupoint sticking TCM nursing technology to fatigue in patients with CHB liver stagnation and spleen deficiency can reduce the patient's fatigue score and TCM syndrome score, improve the symptoms of fatigue and the efficacy of TCM syndrome, reduce the patient's IL-6 index, and improve the patient's quality of life. It is easy to operate, has good patient compliance, can reduce medical costs, and can be popularized and applied in patients with CHB fatigue.