The clinical data of a patient with advanced lung adenocarcinoma in Zhuzhou Central Hospital was retrospectively analyzed and the relevant literatures were reviewed. The patient in study was diagnosed with lung adenocarcinoma by thoracentesis and left lymph node biopsy, and the head MRI and epigastric enhancement CT of upper abdomen showed that the cancer cells had multiple metastasized in the head, liver, spleen, pancreas and left adrenal gland. The genetic testing of epidermal growth factor receptor-amplification refractory mutation system (EGFR-ARMS) was carried out for the patient, which indicated that the exon of EGFR 21 mutation (L858R). The patient’s condition deteriorated after 11 months treatment with the first-generation of EGFR-TKIs, and the result of genetic testing of the patient showed that the EGFR T790M mutation was positive. The attending physician treated the patient with third-generation EGFR-TKIs (osimertinib) for second-line treatment, and the patient’s condition was relieved. After primary EGFR-TKI treatment, patients with advanced adenocarcinoma of the lung are still able to benefit from EGFR-TKI treatment after resistance. The third-generation EGFR-TKIs, represented by osimertinib, has been approved to overcome the EGFR T790M mutation in patients who are resistant to the first- or second-generation TKIs, which brings more survival benefits for patients with advanced NSCLC.