To prolong the survival of the patients, EGFR tyrosine kinase inhibitors (TKIs) resistance in NSCLC is a major challenge that needs to be addressed urgently, and this study focuses on investigating the mechanism of cigarette smoke (CS) induced Gefitinib resistance in NSCLC.<h4>Methods</h4>PC-9 and A549 cells were cultured in vitro and treated with 1 μmol/L Gefitinib for 4 h and 10% cigarette smoke extract (CSE) for 48 h. Here, EGFR is linked to non-small cell lung carcinoma.