Objective: To investigate the diagnostic value of combining determination of ESM-1 and CEA levels in differentiating tuberculous（TPE） from malignant pleural effusion（MPE） caused by lung cancer. Methods: Totally 65 NSCLC patients with MPE and 45 patients with TPE were enrolled into this study. The ESM-1 level in pleural effusion was tested by ELISA and CEA levels were tested by the chemiLuminescence method. All results were analyzed by the statistical method. Results: The levels of ESM-1 and CEA in MPE was significantly higher than those in TPE（P<0.001）. The sensitivity of ESM-1 testing for diagnosing MPE was 81.5%， the specificity was 84.60% and the accuracy was 82.73%. The sensitivity of CEA testing was 73.80%， the specificity was 95.60%， and the overall accuracy was 82.73%. The sensitivity of the combined testing was 83.10%， the specificity was 96.30%， and the overall accuracy was 82.73%. The sensitivity and the overall accuracy of combined testing were higher than those by ESM-1 and CEA testing single. Conclusion: MPE presents higher ESM-1 concentration than TPE does，and determination of ESM-1 is useful to differentiate MPE from TPE. The combined testing of ESM-1 with CEA can increase the sensitivity of diagnosis of MPE.