Objective To explore the cost effectiveness of osimertinib and gefitinib in the treatment of advanced non-small cell lung cancer （NSCLC） with epidermal growth factor receptor （EGFR） mutation. Methods A total of 52 advanced NSCLC patients with EGFR mutation treated by osimertinib were selected as group A from June 2021 to August 2022 at the Chengde Central Hospital, and 52 patients treated by gefitinib were selected as group B according to the propensity score matching method in 1∶1 ratio. The treatment cost and effect of the two groups of patients were compared, and the cost-effectiveness ratio was calculated, and sensitivity analysis was conducted. Results The total effective rate of group A was higher than that of group B （90.38% vs 71.15%, χ²=6.190, P=0.013）. The drug cost and total treatment cost of group A were higher than those of group B（P<0.05）, and other direct costs were lower than those of group B （P<0.05）. The incremental cost effectiveness ratio of group A was 374.71. After the cost-effectiveness sensitivity analysis on adjusting drug costs to decrease by 10% and the total effective rate to decrease by 10% of the two groups, the sensitivity analysis results were basically consistent with the original results. Conclusion Based on the latest prices and actual case data of osimertinib and gefitinib, osimertinib was better than gefitinib in the treatment of advanced NSCLC patients with EGFR mutation. Although gefitinib had lower treatment costs, osimertinib had more cost effectiveness advantages. These findings could provide important reference for the clinical development of treatment plans for advanced NSCLC patients with EGFR mutations.