Abstract: Objective To investigate the correlation between inflammatory cytokines and cancer-related fatigue （CRF） in breast cancer patients undergoing adjuvant radiotherapy. Methods Breast cancer patients receiving postoperative adjuvant radiotherapy were recruited and divided into the fatigue group and observation group according to the fatigue score of Edmonton Symptom Assessment System. The differences of serum inflammatory cytokines of CRP, IL-6 and soluble tumor necrosis factor receptor-2 （sTNFR2） were statistically compared between two groups. The single nucleotide polymorphism of the genes encoding the inflammatory cytokines that were linked to CRF were also detected in each patient, and the relationship between genotyping and fatigue score was analyzed. Results Sixty one patients were enrolled,including 37 patients in the fatigue group and 24 cases in the control group. The incidence of CRF was 60.6%. The number of patients presenting with nausea, anxiety and lack of appetite in the fatigue group was significantly higher than that in the control group （all P < 0.05）. The serum concentration of IL-6 in the fatigue group was significantly increasedafter adjuvant radiotherapy （P < 0.001）, whereas the serum levels of IL-6 did not significantly differ before and after adjuvant radiotherapy in the control group （P > 0.05）. The serum level of IL-6 was positively correlated with the incidence of fatigue （r _s = 0.51, P < 0.001）.The serum levels of CRP and sTNFR2 before and after corresponding treatment did not significantly differ between two groups （all P > 0.05）. Patients with GG genotyping of IL6-174 gene obtained significantly higher fatigue scores after radiotherapy compared with their counterparts with CC genotyping （P = 0.001）. Conclusion Serum IL-6 concentration and GG genotyping of IL6-174 gene are associated with the incidence of CRF in breast cancer patients during adjuvant radiotherapy.