Abstract: A 40-year-old male patient presented with an unexplained pericardial effusion and was treated with antituberculosis therapy. This patient showed a transient improvement, but then progressively worsened to develop constrictive pericarditis, multiple plasma chamber effusions, and venous thrombosis. The patient was transferred to Zhongshan Hospital, Fudan University. Through a pleural histopathological biopsy, this patient was diagnosed with pleural mesothelioma and secondary malignant tumor of the pericardium. Later, clinical the manifestations of patient progressed rapidly, resulting in the death of the patient. Mesothelioma is a very rare group of malignant tumors originating from the pleura and other tissues. Patients are mostly advanced at the time of initial diagnosis, with limited treatments and short median survival. It is important to strengthen the understanding of mesothelioma, pay attention to all medical and technical examinations, especially dynamic follow-up of changes in the disease for early diagnosis of this disease.