Gefitinib, a selective inhibitor of the epidermal growth factor receptor-tyrosine kinase, it's one of the most frequent drug-related adverse effects (AEs) reported in literature is dermatologic AEs. We report, a case of severe cutaneous adverse reactions induced by gefitinib as second-line treatment in a male patient with advanced non-small cell lung cancer after 1 month of treatment. Although tumor shrunk and patient got benefit from the treatment, gefitinib had to be stopped right away. We managed the symptoms of rash with a variety of treatments, including topical ethacridine lactate, antihistamine and so on. After the rash improved, we found his tumor were progress. Then he took gefitinib again without severe skin toxicity or disease progression. We think the development of gefitinib-induced rash may be a sign of effective and administrating it again maybe relieves the degree of rash.