This article reports 1 case of advanced T790M lung adenocarcinoma treated with osimertinib after treatment of epithelial growth factor receptor (EGFR) gene 19 exon deletion mutation and drug resistance with osimertinib. The 72-years-old female presented left chest tightness and asthma for 5 d without obvious inducement and was treated at the local hospital. CT examination of the chest showed bilateral pleural effusion, mid-lobe occupation of the right lung, and mediastinal lymph node enlargement. In order to seek further treatment, she came to the First Affiliated Hospital of Zhengzhou University and was admitted to the hospital to complete relevant examinations. PET-CT showed that the metabolism of soft tissue mass in the middle of the right lung was relatively active. Bilateral supraclavicular area, mediastinum and right hilum multiple lymph node enlargement, metabolic activity, consider metastasis. The first CT-guided percutaneous lung biopsy confirmed lung adenocarcinoma, and the gene test showed that after EGFR gene exon 19 deletion mutation, the patient began to take gefitinib on November 29, 2017 and stopped taking it on December 4, 2018. The results of the second CT-guided percutaneous lung biopsy showed lung adenocarcinoma. The gene test showed EGFR gene 18 exon deletion mutation, and EGFR gene 20 exon T790M mutation. Osimertinib was taken since December 4, 2018, and no abnormality was found.