We found that EHD1 was an important factor in EGFR-TKI resistance and the cancer stem-like cell phenotype of lung cancer, and these results suggest that targeting the NF-κB/miR-590/EHD1 pathway has potential therapeutic promise in EGFR-mutant NSCLC patients with acquired EGFR-TKI resistance. Here, NFKB1 is linked to lung cancer.