To investigate whether expression of several cytokines affected clinical outcome in non-small cell lung cancer patients. A total of 86 stage IIIB/IV non-small cell lung cancer patients, treated with platinum-based doublets, were examined expression levels of IL-1, IL-2R, IL-5, IL-6, IFN-γ, TNF-α pre- and post-chemotherapy. Enzyme-linked immunosorbent assay technique was performed. Kaplan-Meier analysis and Cox regression analyses were used to adjust for possible confounding variables. IL-6 expression levels were significantly decreased due to chemotherapy in patients with stable disease (P=0.041). IL-2R expression levels were significantly increased due to chemotherapy in patients with progression disease (P=0.010). Patients with high concentrations of TNF post-chemotherapy had a significantly longer survival (P=0.009, 17 months versus 11 months) than low levels. Multivariate analysis showed that sex, response rate, IL-1 and TNF-α were significantly predictive of the survival. Serum IL-6 and IL-2R levels correlated with chemoresponse in advanced non-small cell lung cancer, serum IL-1 and TNF-α can be predictive factors in advanced non-small cell lung cancer.