Abstract: Background and purpose: Primary or secondary drug resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKI) is a new challenge in the treatment of advanced non-small cell lung cancer (NSCLC). Osimertinib is a third-generation EGFR-TKI, and its efficacy and safety in NSCLC patients with first-generation EGFR-TKI resistance, especially lung adenocarcinoma, are not yet clear. The purpose of this study was to observe the efficacy and adverse reactions of osimertinib in the treatment of patients with advanced lung adenocarcinoma. Methods: From Apr. 2017 to Sep. 2018, 62 patients with advanced (stage Ⅳ) lung adenocarcinoma were diagnosed in Shanghai Chest Hospital. The diseases were progressed after first-line EGFR-TKI treatment. 88.7% of patients received third-line or more treatment. The efficacy and adverse reactions of osimertinib treatment were observed. Results: Among the 62 patients with advanced lung adenocarcinoma, 25 (40.3%) achieved partial response (PR), 28 (45.2%) had stable disease (SD), and 9 (14.5%) had progressive disease (PD). The objective response rate (ORR) was 40.3% (25/62), the disease control rate (DCR) was 85.5% (53/62), and the median progression-free survival (mPFS) was 10.30 months (95% CI: 9.92-10.68 months). The incidence of adverse events of degree 3 and above was 11.3%. The main adverse events were diarrhea (38.7%) and rash (32.2%), which were significantly alleviated after symptomatic treatment. Conclusion: Osimertinib definitely has a curative effect in the treatment of patients with advanced lung adenocarcinoma, and the incidence of adverse reactions is low.