To examine the outcomes of concurrent versus sequential whole-brain radiotherapy (WBRT) and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in nonsmall cell lung cancer (NSCLC) patients with EGFR mutation.Retrospectively 105 patients with NSCLC, brain metastasis, and EGFR mutation (Affiliated Hospital of Guangdong Medical University, 01/2011 to 12/2014) were grouped as: EGFR-TKIs alone (n = 39, group A), EGFR-TKIs + concurrent radiotherapy (n = 34, group B), and radiotherapy followed by EGFR-TKIs (n = 32, group C).The intracranial objective response rates of groups A, B, and C were 66.7%, 85.3%, and 75%, respectively (P < .05). The median intracranial progression-free survival of groups A, B, and C were 6.8, 12.4, and 9.1 months, respectively (P < .05). The median extracranial progression-free survival of groups A, B, and C were 7.8, 9.4, and 8.3 months, respectively (P > .05).EGFR-TKIs and WBRT by simultaneous application improved the short- and long-term benefits to patients with NSCLC brain metastasis carrying EGFR mutation compared to concurrent application or EGFR-TKIs alone without additional adverse events.