Objective To evaluate the application of combined five tumor markers, CEO, CA125, CA199, NSE and SF in diagnosing lung cancer in terms of enhancement in the early detection rate.Methods Using tumor markers protein chip, the serum CEA, CA125, CA19-9, NSE and SF levels in 73 cases of non-small cell lung cancer (NSCLC), 21 cases of benign pulmonary disease and 16 cases of normal controls were measured and compared.Results The levels of CEA, CA125, CA19-9, NSE and SF in patients with NSCLC were significantly higher than those in the group with benign lung diseases and in the control group( P <0.01). The sensitivity of CEA, CA125, CA19-9, NSE and SF were 79.5%, 56.2%, 56.2%, 52.1%, 57.5%, respectively, and the corresponding specificity 81.0%, 100%, 85.7%, 90.5%, 80.9%, respectively. Moreover, the sensitivity and specificity of the combined determinations including the five tumor markers were higher than those of the respective determination.Conclusion The serum CEA, CA125, CA19-9, NSE and SF levels are very valuable in diagnosis of lung cancer. The combined detection five tumor markers is recommended in clinical work.