Abstract: Objective To evaluate the incidence of cancer-related fatigue(CRF) in patients with advanced lung cancer, and to measure the levels of CRP, IL-6 and CORT to explore the correlation between the indexes and CRF. Methods We used FACIT-F scale to assess the CRF in 51 patients with advanced lung cancer. The serum level of CRP was measured by immunoturbidimetry, the level of CORT was determined by immune particle electro chemiluminescence method, and the IL-6 level was tested by double antibody sandwich enzyme linked immunosorbent assay(ELISA). Spearman correlation analysis was applied to analyze the correlation of score of FACIT-F scale with the level of markers in the serum, and Logistic regression was used to analyze the risk factors. Results The additional concerns subscale score of 27 patients was ≤34 and the incidence of CRF was 52.9%. Physical condition and additional concerns subscale scores of patients with pain were lower than those without pain(P=0.009, P=0.018). Sleep disorders had significant impact on physical condition, additional concerns and total score. Scores of patients with sleep disorders were significantly lower than those without sleep disorders (P<0.01). CRP levels in serum were negatively correlated with physical condition, functional condition, additional attention and total score(P=0.004, 0.027, 0.007, 0.013). IL-6 level was negatively correlated with physical condition, additional attention and total score(P=0.044, 0.029, 0.023). CORT level had no correlation with scale scores. Sleep disorders and pain were independent risk factors for CRF, and OR values were 6.167 and 7.405 (P=0.010, 0.005). Conclusion The levels of IL-6, CRP in serum are significantly associated with the degree of fatigue; the higher levels of IL-6 and CRP are, the more significant correlation is. CRP and IL-6 could be used as clinical monitoring indexes of fatigue. Patients with pain and sleep disorder are more prone to fatigue, and the fatigue degree is more serious.