OBJECTIVE：To evaluate the economic s of osimertinib versus first-generation EGFR-TKIs in the first-line treatment of EGFR mutation-positive locally advanced or metastatic non-small cell lung cancer （NSCLC），and to provide evidence-based reference for medical and healthy decision-making in China. METHODS ：From respective of health care system ，Markov model was developed by using patientsurvival data and published literature datato simulate 10 years of direct medical costs and quality-adjusted life years （QALY）for EGFR mutation-positive locally advanced or metastatic NSCLC patients ，with a model cycle length of 3 weeks，and the discount rate of 5％. One-way sensitivity analysis and probabilistic sensitivity analysis were used to evaluate the effects of parameter changes on the stability of the model results. RESULTS ：In the base-case analysis ，compared with the first-generation EGFR-TKIs ，osimertinib could obtain 0.40 QALYs more ，with an incremental cost of 163 531.55 yuan and an incremental cost-utility ratio （ICER）of 409 321.54 yuan/QALY，which was higher than the willingness-to-pay （WTP）threshold in China（3 times per capita GDP in China in 2019 of 212 676 yuan/QALY）. The results of one-way sensitivity analysis showed that the utility value of progression-free survival status and the price of osimertinib had the greatest impact on ICER. The results of probability sensitivity analysis showed that the probability of osimertinib to be cost-effective was 11.00％ at the WTP threshold in China. When the price of osimertinib decreased by 30％，50％ and 70％，the probability of osimertinib to be cost-effective was 26.20％，47.40％，and 74.30％ at the WTP threshold of 212 676 yuan/QALY，respectively. CONCLUSIONS ：When Chinese 3 times per capita GDP in 2019 is used as the criterion for judgment ，osimertinib is not economical compared with the first-generation EGFR-TKIs in first-line treatment of locally advanced or metastatic NSCLC with EGFR mutation-positive. Appropriate price reduction can improve its economy.