Abstract: Objective To investigate the significance of hypoxia inducible factor-1α（HIF-1α） and vascular endothelial growth factor （VEGF） in differential diagnosis of tuberculous and lung cancer with malignant pleural effusion. Methods From 108 patients with pleural effusion in our hospital from January 2012 to December 2013， 45 patients were enrolled and divided into lung cancer with pleural effusion （CA group， n=25） and tuberculous pleural effusion group （TB group， n=20） according to the pleural effusion property. The levels of HIF-1a and VEGF in serum and pleural fluid were measured in two groups， and the ratio of hydrothorax to serum VEGF （hydrothorax／serum VEGF） and the ratio of hydrothorax to serum HIF-1α （hydrothorax／serum HIF-1α） were calculated. The receiver operating characteristic curve （ROC） was used to analyze the efficacy of HIF-1a， VEGF， hydrothorax／serum HIF-1a and hydrothorax／serum VEGF in differentiating lung cancer with malignant pleural effusion from tuberculous pleural effusion. The sensitivity， specificity and diagnostic accuracy of the different combination patterns of hydrothorax HIF-1a， serum HIF-1a， hydrothorax VEGF and serum VEGF were analyzed. Results The hydrothorax level of HIF-1a in the CA group was （2.29±0.89） ng／ml， higher than （0.88±0.69） ng／ml in TB group， and the difference was statistically significant （P<0.01）. The serum level of HIF-1a in CA group was （2.00±1.00） ng／ml， similar with （1.85±0.77） ng／ml in TB group （P＞0.05）. The level of hydrothorax levels of VEGF were （1035.31±687.64） pg／ml and （732.97±493.61） pg／ml and serum levels of VEGF were （491.25±278.33） pg／ml and （463.42±288.15） pg／ml in CA group and TB group （P＞0.05）. The level of hydrothorax／serum HIF-1α in CA group was 1.26±0.49， higher than 0.56±0.55 of TB group， and the difference was statistically significant （P<0.01）. The levels of hydrothorax／serum VEGF were 2.85±2.73 and 2.02±1.58 in CA group and TB group， and the difference was not statistically significant （P＞0.05）. In differential diagnosing malignant and tuberculous pleural effusion， the sensitivity and specificity were 88% and 85% for HIF-1α alone， 92% and 85% for hydrothorax／serum HIF-1α alone， and 64% and 100% for HIF-1α and VEGF in serum and pleural effusion. Conclusion Both levels of HIF-1α in pleural effusion and pleural effusion／serum HIF-1α have certain value in the differential diagnosis of malignant and tuberculous pleural effusion. The joint detection HIF-1α and VEGF in serum and pleural effusion can improve specificity.