Gefitinib and erlotinib are first-generation small molecular inhibitors of EGFR tyrosine kinase activity. To the best of our knowledge, to date, two reports have stated that patients with NSCLC who develop severe hepatotoxicity secondary to gefitinib treatment can be safely switched to erlotinib. However, the reverse situation has not been reported. Here, we present the first case with non-small cell lung cancer harboring EGFR mutation who developed grade 3/4 hepatotoxicity after initiation of erlotinib, which resolved when therapy was changed to gefitinib. As far as we know, this is the first report showing the efficacy of gefitinib for a non-small cell lung cancer patient who developed severe hepatotoxicity while under erlotinib therapy.