Objective: To evaluate the association of a diagnosis of lung cancer and combined detection of serum carcinoembryonic antigen (CEA), carbohydrateantigen 19-9 (CA19-9), neuron specific enolase (NSE) as well as the cytokeratin 19 fragment (CYFRA21-1). Methods: Serum CEA, CA19-9, NSE and CYFRA21-1 were assessed in 150 patients with lung cancer, 100 patients with benign lung disease and 100 normal control subjects, and differences of expression were compared in each group, and joint effects of these tumor markers in the diagnosis of lung cancer were analyzed. Results: Serum CEA, CA19-9, NSE and CYFRA21-1 in patients with lung cancer were significantly higher than those with benign lung disease and normal controls (p<0.01). It is suggested that these four tumor markers combined together could produce a positive detection rate of 90.2%, significantly higher than that of any single test. Conclusion: Combination detection of CEA, CA19-9, NSE and CYFRA21-1 could significantly improve the sensitivity and specificity in diagnosis of lung cancer, and could be important in early detection.