Abstract: Objective To investigate the therapeutic effect of video-assisted thoracoscopic lobectomy combined with radiotherapy and chemotherapy for elderly patients with non-small cell lung cancer（NSCLC）and its effect on transforming growth factor-β₁（TGF-β₁）and hypoxia inducible factor-1α（HIF-1α). Methods A total of 96 elderly patients with NSCLC were randomly selected and divided into control group and observation group according to the random number table,48 cases in each group.The patients in the observation group received radiotherapy and chemotherapy before video-assisted thoracoscopic lobectomy,while those in the control group received video-assisted thoracoscopic lobectomy.The therapeutic effect,serum levels of TGF-β₁,HIF-1α and complications were observed in the two groups. Results There was no significant difference in the levels of TGF-β₁,and HIF-1α between the two groups before treatment（P＞0.05）.After treatment,the levels of TGF-β₁ and HIF-1α in the two groups decreased significantly,and the decrease in the observation group was more significant（P＜0.05）; there was no significant difference in the incidence of complications between the two groups（P＞0.05）.The 2-year follow-up showed that the survival rate of the observation group（91.67%）was significantly higher than that of the control group（81.25%）,and the difference was statistically significant（P＜0.05）. Conclusions Video-assisted thoracoscopic pulmonary lobectomy combined with radiotherapy and chemotherapy is effective in the treatment of elderly patients with NSCLC and in reducing the levels of TGF-β₁,and HIF-1α,which can be widely used in clinical practice.