Abstract: Objective: To detect hTERT mRNA, CEA, and CA19-9 in pleural fluids and to explore their significance in the differential diagnosis of malignant and benign effusions. Methods: The concentrations of CEA and CA19-9 in pleural fluids were measured by automated chemiluminescence and the expression of hTERT mRNA was detected by RT-PCR. Results: The positive rates of hTERT mRNA, CEA and CA19-9 were significantly higher in the malignant group than in the benigh group (P<0.05). The sensitivity, specificity and diagnostic accordance rate (%) of the three tumor markers were as follows: hTERT mRNA: 81.8%, 90.5%, and 86.1%; CEA: 52.3%, 92.9%, and 72.1%; CA19-9: 34.1%, 90.5%, and 61.6%. The positive rate of hTERT mRNA combined with CEA was 97.7%. Conclusion: Detection of hTERT mRNA, CEA, and CA19-9 can be helpful for the differential diagnosis of pleural effusions. The combined detection of hTERT mRNA and CEA in pleural effusions is a more helpful method.