BACKGROUND: The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), became an attractive therapeutic option for advanced non-small-cell lung cancer (NSCLC). Several studies suggested that there might be some different efficacy or response predictors between gefitinib and erlotinib. We compared the efficacy and toxicity of gefitinib and erlotinib in Korean patients with advanced NSCLC and evaluated specific predictors of response for both gefitinib and erlotinib. METHODS: We collected the clinical information on patients with advanced NSCLC, who were treated with gefitinib or erlotinib at the Ewha Womans University Hospital, between July 2003 and February 2009. Median survival times were calculated using the Kaplan-Meier method. RESULTS: Eighty-six patients (52 gefitinib vs. 34 erlotinib) were enrolled. Patient median age was 64 years; 53 (62%) subjects were male. Out of the 86 patients treated, 83 received response evaluation. Of the 83 patients, 35 achieved a response and 12 experienced stable disease while 36 experienced progressive disease, resulting in a response rate of 42% and a disease control rate of 57%. After a median follow-up of 502 days, the median progression-free and overall survival time was 129 and 259 days, respectively. Comparing patients by treatment (gefitinib vs erlotinib), there were no significant differences in the overall response rate (44% vs. 39%, p=0.678), median survival time (301 days vs. 202 days, p=0.151), or time to progression (136 days vs. 92 days, p=0.672). Both EGFR-TKIs showed similar toxicity. In a multivariate analysis using Cox regression model, adenocarcinoma was an independent predictor of survival (p=0.006; hazard ratio [HR], 0.487; 95% confidence interval [CI], 0.292-0.811). Analyses of subgroups did not show any difference in response predictors between gefitinib and erlotinib. CONCLUSION: Comparing gefitinib to erlotinib, there were no differences in the response rate, overall survival, progression-free survival, or toxicity. No specific predictor of response to each EGFR-TKI was identified.