We reported a male, 64-year-old patient who suffered advanced lung adenocarcinoma admitted to The Fourth Hospital of Hebei Medical University. On April 22, 2017, he was sent to our department due to cough and chest tightness. His chest CT revealed plenty of left pleural effusion. The pleural effusion cells biopsy reported malignancy, possibility of lung adenocarcinoma. Positiron emission tomography-computed tomography (PET-CT) showed slightly thickening of the left pleura, local pleural nodular abnormal glucose high metabolism. After thoracoscopic pleural biopsy, further diagnosis of cancer (considering pulmonary origin) was confirmed. The immune-cytology of pleural effusion also showed adenocarcinoma, considering the pulmonary origin. The gene analysis revealed EGFR 19del positive. So, he was given EGFR-TKI erlotinib regularly. After 14 months stable conditions, on June 30, 2018, this patient was admitted to our hospital again, due to chest tightness. The pulmonary ultrasound showed big liquid dark area (about 10.1 cm diameter) in his left thoracic cavity. Immediately, a thoracic drainage tube was placed in, then from which about 700 mL of dark blood pleural effusion was induced out. The cytology analysis found cancer cells. And the gene test results T790M positive. So, the third-generation EGFR-TKI Osimertinib was administrated to him on July 9, 2018. All patient’s clinical symptoms were disappeared and his condition was stable until now.