Survivin and X-linked inhibitor of apoptosis (XIAP) are two inhibitors of apoptosis that are expressed highly in most malignancies and may be diagnostic markers of cancer. The aim of this study was to assess the diagnostic value of survivin and XIAP as tumor markers in malignant pleural effusion. Ninety-eight consecutive patients (including 56 malignant effusions and 42 benign effusions) with pleural effusion were enrolled in the study. Levels of survivin and XIAP mRNA in pleural fluid were measured by reverse transcription polymerase chain reaction. Carcinoembryonic antigen (CEA) was also detected simultaneously. Results showed that levels of survivin and XIAP mRNA were significantly higher in malignant than in benign effusion (P < 0.001 and P = 0.002, respectively). In the diagnosis of malignant pleural effusion, survivin achieved the highest sensitivity (89.3 %) and specificity (95.2 %), as compared with XIAP (66.1 % sensitivity and 85.7 % specificity), or CEA (71.4 % sensitivity and 80.9 % specificity). The combination of survivin and CEA reached 94.6 % sensitivity, with 90.5 % specificity, whereas the combined analysis of survivin and XIAP yielded the highest specificity (95.2 %) and a very good sensitivity (91.1 %). In conclusion, survivin mRNA assay is a useful tumor marker for discriminating malignant from benign pleural effusion. XIAP may be a good candidate for molecular detection of malignant effusion. The combination of survivin and CEA, or XIAP, can increase diagnostic performance.