We retrospectively compared the efficacy of standard platinum-based chemotherapy with that of combination chemotherapy using vinorelbine (VNR) plus dihydropyrimidine dehydrogenase-inhibitory fluoropyrimidine (DIF) in EGFR-mutated lung adenocarcinomas, and we investigated a potential mechanism by which the combination chemotherapy of VNR + DIF was favorable in the treatment of EGFR-mutated lung adenocarcinoma in vitro. The gene discussed is EGFR; the disease is lung adenocarcinoma.