Purpose: To compare the differences in survival and intracranial local control between patients treated with whole-brain radiotherapy (WBRT) and WBRT plus a radiotherapy boost (RTB) in non-small-cell lung cancer (NSCLC) patients with brain metastases (BMs). Patients and methods: Between May 2010 and October 2017, 206 NSCLC patients with BMs were treated with brain radiotherapy; among these patients, 140 patients underwent WBRT alone (group A) and 66 patients underwent WBRT plus RTB (group B). The endpoints included intracranial local progression-free survival and regional progression-free survival time (iLPFS and iRPFS, respectively) and overall survival (OS). Results: Between the two groups, not all baseline clinical factors were well-balanced. The median iLPFS was 17.9 months in group A and 22.3 months in group B. The 2-year iLPFS rates were significantly lower in group A than in group B (34.5% vs 49.3%, P=0.041); however, no significant differences were observed in OS or iRPFS. Multivariate analyses revealed that epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) therapy was significantly associated with good OS, iLPFS, and iRPFS. Among the patients treated with TKIs (n=62), there were no differences in OS (P=0.190), iLPFS (P=0.334), or iRPFS (P=0.338) between groups A and B. In the patients without TKI treatment (n=102), the median iLPFS was significantly longer in group B than in group A (16.7 vs 12.0 months, P=0.032), but no significant differences were found in OS (p=0.182) or iRPFS (P=0.837) between the two groups. Conclusion: WBRT plus RTB significantly improved iLPFS compared with WBRT alone, especially in patients without EGFR-TKI treatment. However, there were no significant differences in iRPFS or OS between the two groups. Patients treated with EGFR-TKIs may not benefit from WBRT plus RTB.