Background: Tuberculous pleurisy is inflammation caused by direct infection of Mycobacterium tuberculosis (MTB) and/or delayed allergic reaction of the pleura to MTB thallus components. The diagnosis of tuberculous pleurisy is mainly confirmed by bacterial culture, smear staining or histopathology, but has some clinical limitations. Next-generation sequencing (NGS), as a new diagnostic technology, has good application prospects in the diagnosis of tuberculous pleurisy. Case Presentation: A patient admitted with right pleural effusion and pneumonia was actively treated with anti-infection, anti-inflammatory and symptomatic support while various etiological tests of right pleural effusion were improved. However, all the etiological tests for MTB infection were negative. At this time, the patient's condition worsened and pleural effusion also appeared on the left side. In order to clarify the cause of the disease as soon as possible and prevent the disease from worsening again, the left and right pleural effusions of the patient were sent for NGS testing. The test results suggested MTB infection, which finally clarified the diagnosis of tuberculous pleurisy, and the next treatment plan of the patient was timely adjusted. Conclusion: NGS is instructive in the diagnosis of tuberculous pleurisy when various conventional tests and imaging methods fail.