Abstract: Objective To explore the value of combined detection of CEA, NSE and CYFRA21-1 in differential diagnosis of hydrothorax with serum and hydrothorax. Methods The hydrothorax and serum CEA, NSE and CYFRA21-1 levels in 42 lung cancer and 65 pneumonia patients were detected by double-antibody sandwich chemoluminescence. Results The hydrothorax and serum level of CEA, NSE and CYFRA21-1 in the lung cancer patients were significantly higher than that of pneumonia group (P<0.01). The sensitivity and accuracy of combined CEA, NSE and CYFRA21-1 were higher than each sigle test Conclusion The sensitivity and accuracy of combined detection of CEA, NSE and CYFRA21-1 in serum and hydrothorax are remarkably higher than each single test. The detection of hydrothorax was more valuable than the serum detection.