Rationale:Spontaneous hemothorax is a subcategory of hemothorax which can be life threatening. The etiology of spontaneous hemothorax can be various, and in some rare cases the causes remained unknown. Hence, it is quite difficult to establish the diagnosis. Here, we report a case of spontaneous hemothorax in a young female patient who was recently diagnosed with anti-N-methyl-d-aspartate receptor encephalitis (anti-NMDAR encephalitis).Patient concerns:A 20-year-old female was transferred to emergency department of our hospital from local hospital presented with insomnia, mood lability, tonic-clonic seizure, and decreased level of consciousness.Diagnoses:The diagnosis of anti-NMDAR encephalitis was established by detection of cerebrospinal fluid (CSF) and serum antibodies to the NMDA receptor. During the hospital stay, the patient developed massive spontaneous hemothorax and was confirmed by closed-tube thoracostomy.Interventions and outcomes:Video-assisted thoracotomy was performed to evacuate the blood clots and also to obtain pleural biopsy specimen for diagnostic evaluation. However, the reason of hemothorax remained idiopathic. The postoperative status of this patient was uneventful, and she was discharged on postoperative day 45 as her mental status improved markedly.Lessons:In this case, the patient had both anti- NMDAR encephalitis and autoimmune thyroid disease. Based on it, we suspected that the patient subjected to severe autoimmune response and inflammatory reaction, which might explain the pathologic changes of parietal pleura and visceral pleura. We recommend the suspicion of spontaneous hemothorax should be considered when the patients with autoimmune diseases present with hemorrhage-related signs or symptoms.