Background: To investigate the expression of TNF-α, IL-6, IL-10 in the plasma of patients with lung cancer who received radiation therapy (RT), and to analyze the correlation between these cytokines and radiation pneumonitis (RP). Materials and Methods: Patients with lung cancer who received 3D-CRT in our hospital were prospectively evaluated. Circulating cytokine levels were measured with ELISA before RT and at the end of RT. Regular follow-up was undertaken 3 months after RT. Statistical analysis was applied to determine the relevance of cytokines to radiation-induced lung injury. Results: Of 104 patients, 29 (27.9%) developed RP. The levels of TNF-α and IL-6 levels in the plasma after RT were significantly higher than before RT (p<0.05), whereas IL -10 levels were significantly lower after RT than before RT (p<0.05). Before RT, TNF-α levels were higher in RP group (p<0.05),but there were no differences in TNF-α levels after RT. No association was observed between IL-6 and IL-10 levels and the risk of RP. Univariate analysis showed that baseline pulmonary function, smoking history, histopathology, lung volume receiving ≥20 Gy (V20), Mean lung dose (MLD) and total radiation dose were related to RP, but only MLD was an independent risk factor for RP in lung cancer patients (OR>1). Conclusion: TNF-α levels in plasma were closely related to RP but still cannot be used as predictors for RP.