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To determine the cause of malignant pleural effusion is important for treating and managing malignant pleural effusion,especially cause of unknown primary.Now,there are still limited biomarkers for predicting the cause of malignant pleural effusion in clinical practice.Hence,we evaluated five (CEA,AFP,CA125,CA153 and CA199) tumor biomarkers diagnostic value in predicting the cause of malignant pleural effusion in a retrospective study.Kruskal–Wallis test or Mann-Whitney U test were carried out to compare levels of tumor markers in pleural effusion between different causes of malignant pleural effusion.