Since HGF/MET was previously identified as playing a critical role in the resistance mechanism of EGFR-TKIs in EGFR mutant NSCLC, we investigated whether HGF also influenced EGFR-TKI sensitivity in lung adenocarcinoma cells harboring wild-type EGFR. We found that HGF significantly reduced sensitivity to gefitinib through the PI3K/Akt and MAPK pathways in lung cancer cells with wild-type EGFR. A MET inhibitor, PHA-665752, completely restored the sensitivity to EGFR-TKI. The gene discussed is HGF; the disease is lung cancer.