〔Abstract〕 Objective To investigate the clinical efficacy of gefitinib combined with metformin in the treatment of non-small cell lung cancer. Methods A total of 98 patients with non-small cell lung cancer admitted by Yuzhou People's Hospital from January 2018 to January 2020 were selected. According to the random number table method, they were divided into two groups with 49 cases in each. The control group was treated with gefitinib, the observation group was treated with gefitinib combined with metformin. The total response rate, survival, quality of life and changes of serum tumor markers were compared between the two groups. Results After treatment, the total effective rate of the observation group was 85.71%, which was higher than 63.27% of the control group, and the difference was statistically significant (P < 0.05). The progression-free survival time and overall survival time in the observation group were longer than those in the control group, and the levels of cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) and carcino-embryonic antigen (CEA) in the observation group were lower than those in the control group, and the Karnofsky performance status (KPS) score and functione assessmentof cancer therapy-L (FACT-L) score in the observation group were higher than those in the control group, the differences were statistically significant (P < 0.05). ConclusionIn the treatment of non-small cell lung cancer, compared with gefitinib alone, gefitinib combined with metformin improves the efficacy, prolongs the survival time of patients, improves the quality of life, and reduces the level of serum tumor markers.