Background and objective Non-small cell lung cancer (NSCLC) presents the highest morbidity and mortality among malignant tumors worldwide. hTe overall effective rate of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is 30% to 40%, and PFS (progression-free sruvival) is 12 months. However, EGFR-TKI resistance is typical in clinical observations, and this phenomenon signiifcantly affects tumor suppression. To overcome this resistance, a new prognostic factor associated with lung cancer drug resistance should be discovered. This study investigated the rela-tionship between the inhibitor of differentiation 1 (ID1) and non-small cell lung cancer EGFR-TKI resistancein vivo andin vitro to determine any statistical signiifcance and discuss the underlying mechanism.Methods Western blot and qRT-PCR were used to quantify the expression of ID1 in lung cancer. IHC was used to detect the expression of ID1 in pathological tissues (lung cancer tissues and adjacent tissues). MTT was used to detect cell proliferation, in which the cells were treated with geiftinib atfer being transfected by ID1 slow virus vector. Lung cancer cells were inoculated in nude mice until the tu-mor diameter grew to certain measurement. Geiftinib treatment was started, and the tumor volume was estimated.Results ID1 was highly expressed in NSCLC (P<0.05). Both ID1 expression and drug resistance of EGFR-TKI in NSCLC were positively correlated (P<0.05). hTe treatment group with geiftinib showed obviously less expression than the control group. Conclusion ID1 is highly expressed in NSCLC. ID1 expression was positively related to drug resistance of EGFR-TKI in NSCLC. Geiftinib can be used to effectively treat NSCLC, and the mechanism may be associated with an increased level of STAT3 phosphorylation.