Abstract: Objective To investigate the clinical efficacy of first-line osimertinib in the treatment of advanced epidermal growth factor receptor （EGFR）-mutated non-small cell lung cancer （NSCLC） patients. Methods Thirty-five EGFR-mutated patients with advanced NSCLC diagnosed in the Guangdong Provincial People's Hospital from June 2017 to January 2020 were retrospectively analyzed. The objective response was evaluated according to Response Evaluation Criteria in Solid Tumors （RECIST） 1.1, and the progression-free survival （PFS） was also calculated. Results Among the 35 patients, 22 achieved partial response, 5 with stable disease, and 6 with progressive disease. The objective response rate was 63% （22/35）, and the disease control rate was 77%（27/35）. The median PFS was 14.2 months （95% confidence interval, 10.2~18.3 months）. Conclusions First-line osimertinib was effective in advanced EGFR-mutated NSCLC patients in clinical practice.