Here, we found that EHD1 is an important factor in EGFR-TKI resistance and the cancer stem-like cell phenotype of lung cancer, which suggests that targeting the NF-κB/miR-590/EHD1 pathway offers potential therapeutic promise for NSCLC patients with EGFR-mutations and acquired EGFR-TKI resistance. This evidence concerns the gene EGFR and non-small cell lung carcinoma.