A case of non-small cell lung cancer with soft meninges metastasis and coma was admitted to Oncology Department of Second Affiliated Hospital of Nanchang University. The patient, a 55-year-old woman, had a cough after a cold. Chest CT showed left lung mass. CT-guided percutaneous lung biopsy showed lung adenocarcinoma, immunohistochemical showed CK (+), NapsinA (+), TTF-1 (+), ALK-D5F3 (−), Ki-67 was about 15% (+). EAR gene detection: EGFR 19 deletion mutation, ALK (−), ROS1 (−). Further examination showed liver and bone metastases and Iressa targeted therapy was used. One year later, dizziness and headache with somnolence and disturbance of consciousness appeared. Whole brain spinal cord MRI showed brain parenchyma and leptomeningeal metastasis. Cerebrospinal fluid cytology showed adenocarcinoma cells, cerebrospinal fluid gene detection was negative. The symptoms of the patients were significantly relieved after Osimertinib combined with Bevacizumab combined with whole brain and cervical spinal canal radiotherapy. The performance status (PS) score of the patient was 1, PFS of leptomeningeal metastasis treatment has reached 15 months, and is still being followed up. The prognosis of leptomeningeal metastasis of lung cancer is poor, so how to diagnose early and optimize its individualized treatment strategy is worth exploring.