OBJECTIVE: To explore the clinical efficacy of osimertinib in targeted therapies of patients with non-small cell lung cancer (NSCLC), thus providing experimental data for clinical treatment of this disease. STUDY DESIGN: A total of 120 patients with NSCLC who underwent treatment in our hospital between November 2020 and August 2021 were enrolled. These patients were divided randomly into platinum-pemetrexed chemotherapy group (PP) (n=6) and osimertinib targeted therapy group (OT) (n=6). A CT scan was employed for examining patients before and after treatment, and the occurrence of adverse reactions was recorded. The levels of tumor-related markers in serum including carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), neuron-specific enolase (NSE), and carbohydrate antigen 125 (CA125) were compared before and after treatment. Flow cytometry was used to detect the proportion of CD3+, CD4+, and CD8+ T lymphocyte subsets in peripheral blood of patients. Kaplan-Meier method was used to calculate the survival of patients after treatment. RESULTS: There was no significant difference in the general data between the 2 groups. According to CT imaging, as compared with the PP group, tumor volume was decreased significantly in the OT group. After treatment, the tumor-related markers in the serum and adverse reactions in the OT group were significantly less than those of the PP group; also, the proportions of CD3+, CD4+, and CD8+ T lymphocytes were higher than those of the PP group. Compared with the PP group, the survival of patients after treatment was high-er in the OT group. CONCLUSION: Osimertinib (a targeted therapy) shows better efficacy than platinum-pemetrexed (a chemotherapy) in the treatment of NSCLC and has a good therapeutic prospect. (Anal Quant Cytopathol Histpathol 2021;43:879-887) © Science Printers and Publishers, Inc. © 2021 Science Printers and Publishers Inc.. All rights reserved.