Objective To investigate the influence of radiotherapy with concurrent oral epidermal growth factor receptor ( EGFR) and tyrosine kinase inhibitor ( TKI) for advanced non-small cell lung cancer ( NSCLC) on the incidence of interstitial lung disease ( ILD ) , and to analyze the risk factors for the pathogenesis of ILD. Methods The incidence of ILD in 72 patients with NSCLC who were admitted to Department of Radiotherapy Oncology of Lu′an Hospital of Traditional Chinese Medicine and treated with radiotherapy with concurrent oral EGFR-TKI from January 2010 to January 2014 was analyzed retrospectively,and some patients were selected as controls to compare the difference in the incidence of ILD between the TKI concurrent radiotherapy group and the other groups. The univariate analysis using chi-square test and multivariate logistic regression analysis were applied to analyze the risk factors for the incidence of ILD in the patients receiving TKI concurrent radiotherapy. Results The TKI concurrent radiotherapy group had a significantly higher incidence rate of ILD than the palliative chemotherapy group,single TKI group,and concurrent chemoradiotherapy group ( 19. 4% vs. 2. 5%, 12%, and 7. 5%, P= 0. 045 ) . The multivariate regression analysis showed that male sex,long-term smoking,underlying lung disease,tumor volume>5 cm, and application of conventional radiotherapy were the risk factors for the pathogenesis of ILD in the TKI concurrent radiotherapy group. Conclusions Radiotherapy with concurrent TKI for advanced NSCLC may increase the incidence of ILD.