Epidermal growth factor receptor (EGFR) is one of the most common driving genes of lung cancer. Oral therapy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) (gefitinib, icotinib, afatinib, etc.) has shown good efficacy in first-line patients with positive EGFR mutations. However, most patients will develop T790M mutation after taking the initial first-line TKIs treatment, leading to drug resistance and disease progression. One patient with positive EGFR mutation in our department developed disease progression after 1 year of oral treatment with gefitinib tablets. After gene testing, T790M mutation was found to be positive, and oral osimertinib was modified. At present, the efficacy evaluation of the patient is partial remission. Osimertinib has a stable effect in the treatment of patients with T790M mutation. Early and timely combination of clinical, pathological and molecular diagnostic techniques for the entire management of patient treatment can provide a strong guarantee for the treatment of patients with advanced non-small cell lung cancer.