Background: Pleural effusions can be caused by various diseases, making their diagnosis challenging. Light's criteria are often used to distinguish transudative and exudative effusions. Exudative effusions have a more complex etiology, including parapneumonic, tuberculous, and malignant effusion. Objectives: The main objective of this study was to evaluate the effectiveness and sensitivity of Interleukin IL-36γ as a diagnostic marker for differentiating between malignant and infectious pleural effusions. Methods: The study involved 100 patients with pleural effusion. Patients were categorized into five groups based on their final diagnosis. An ELISA technique was used to quantitatively measure the levels of pleural fluid IL-36γ. Results: The results showed that pleural IL-36γ levels were higher in tuberculous pleural effusion compared to malignant, transudative, and uncomplicated pleural effusion. In contrast, pleural IL-36γ levels were higher in complicated pleural effusion compared to tuberculous, malignant, transudative, and uncomplicated pleural effusion. Conclusion: It was concluded that pleural IL-36γ is a novel biomarker that can be used to diagnose and differentiate malignant pleural effusion from infectious pleural effusion.