Objective To investigate the clinical application of acupoint sticking combined traditional Chinese medicine foot bath for the treatment of chronic fatigue syndrome (CFS). Methods According to the random table method, 91 CFS patients were divided into control group (n=45) and the research group (n=46). The patients in the control group were treated with western medicine and acupoint application, while the patients in the research group were treated with Chinese medicine foot bath on the basis of control group. Two groups of patients were treated for 30 consecutive days. The clinical total effective rate of two groups of patients after treatment was assessed. The Pittsburgh sleep quality index scale (PSQI), BELL's chronic fatigue syndrome integral table and fatigue rating scale (FS-14) were determined respectively before and after treatment, at the same time, the levels of serum interleukin IL-1β, IL-6, IL-2 and interferon IFN-λ were detected respectively before and after treatment. In addition, the adverse reactionincidence and recurrence rate of two groups of patients were observed Results The total effective rate of research group was 91.3% (42/46), whilethe total effective rate of control group was 71.1% (32/45). The difference between two groups was statistically significant(χ 2=6.106,P=0.014).After treatment,the PSQI(3.65 ±0.71 vs.4.77 ±0.62,t=-8.008),FS-14(6.16 ±1.52 vs.8.03 ± 1.43,t=-6.042),IL-1β(3.28 ± 0.63 pg/ml vs.(6.86 ± 1.14)pg/ml,t=-18.595)] and IL-6 (20.03 ± 5.79 pg/ml vs. 24.85 ± 6.88 pg/ml, t=-3.619) of research group were significantly lower than the control group (P<0.05), while the BELL's (66.71 ± 12.79 vs.50.62 ± 10.22,t=-6.621), IL-2 (32.96 ± 6.57 pg/ml vs.26.78 ± 6.01 pg/ml, t=4.679)and IFN-λ(36.27 ± 6.71 pg/ml vs.25.63 ± 5.89 pg/mL,t=8.032)of research group were significantly higher than the control group (P<0.05). No serious adverse reactions occurred during the treatment of both groups. The recurrence rate of control group was 25.0% (8/32), which was significantly higher than the research group of 7.1% (3/42) (χ2=4.576, P=0.032). Conclusions The clinical curative effect of acupoint sticking combined Chinese medicine foot bath on the treatment for CFS is significantly, which can significantly improve the patient's quality of sleep and fatigue index, at the same time improve the serum level of inflammatory factors.