Abstract Background The pleura is a serous membrane that surrounds the lungs. The visceral surface secretes fluid into the serous cavity and the parietal surface ensures a regular absorption of this fluid. If this balance is disturbed, fluid accumulation occurs in the pleural space called “Pleural Effusion”. Today, accurate diagnosis of pleural diseases is becoming more critical, as advances in treatment protocols have contributed positively to prognosis. Our aim is to perform computer-aided numerical analysis of Computed Tomography (CT) images from patients showing pleural effusion images on CT and to examine the prediction of malignant/benign distinction using deep learning by comparing with the cytology results. Methods The authors classified 408 CT images from 64 patients whose etiology of pleural effusion was investigated using the deep learning method. 378 of the images were used for the training of the system; 15 malignant and 15 benign CT images, which were not included in the training group, were used as the test. Results Among the 30 test images evaluated in the system; 14 of 15 malignant patients and 13 of 15 benign patients were estimated with correct diagnosis (PPD: 93.3%, NPD: 86.67%, Sensitivity: 87.5%, Specificity: 92.86%). Conclusion Advances in computer-aided diagnostic analysis of CT images and obtaining a pre-diagnosis of pleural fluid may reduce the need for interventional procedures by guiding physicians about which patients may have malignancies. Thus, it is cost and time-saving in patient management, allowing earlier diagnosis and treatment.