Background Periostin (POSTN) is an extracellular matrix protein that is overexpressed in lung cancer and is considered an effective diagnostic and prognostic biomarker for lung cancer. The purpose of this study was to investigate the diagnostic performance of POSTN and to further evaluate the diagnostic value of POSTN combined with carcinoembryonic antigen (CEA) and cancer ratio [CR: serum lactate dehydrogenase (LDH)/pleural effusion adenosine deaminase (PE ADA)] in lung cancer‐related malignant PE (MPE). Methods A total of 108 patients with PE, including 54 with lung cancer and 54 with benign lung disease, were enrolled in this study. The POSTN levels of PE and serum were detected using an enzyme‐linked immunosorbent assay. Information on the expression of PE and serum CEA, serum LDH, and PE ADA was collected from medical records. Results The levels of PE POSTN in MPE of patients with lung cancer were significantly higher than those in patients with benign PE (p < 0.0001). The receiver operating characteristic (ROC) curve indicated that the diagnostic sensitivity and specificity of PE POSTN for lung cancer‐related MPE were respectively 77.78% and 68.52% when the cutoff value was determined to be 53.45 ng/ml. The ROC curve analysis demonstrated that PE POSTN has a high diagnostic value in MPE associated with lung cancer [area under the curve (AUC) = 0.764], and the combination of PE POSTN, PE CEA, and CR can improve the diagnostic accuracy of lung cancer‐related MPE (AUC = 0.948). Conclusion POSTN can be used as a potential marker for lung cancer‐related MPE diagnosis.