Liquid biopsy with cerebrospinal fluid (CSF) is a new approach, which has been used successfully in improving the diagnosis and characterization of LM.[3] NSCLC with EGFR sensitive mutation (SM) could acquire resistance to first-line osimertinib through C797S mutation, which might respond to first- or second-generation EGFR inhibitors.[4–6] Herein, we reported a patient with NSCLC acquired resistance to first-line osimertinib. This evidence concerns the gene EGFR and non-small cell lung carcinoma.