In this study, the volume response and treatment outcome after hippocampus-sparing whole-brain radiotherapy (HS-WBRT) with simultaneous integrated boost (SIB) using tomotherapy were evaluated. Patients with primary lung adenocarcinoma and multiple brain metastases who had a Karnofsky performance status ≥70 and exhibited well-controlled extracranial disease were treated. The prescribed dose was administered in 10 to 14 fractions as 25 to 28 Gy to whole-brain parenchyma, as 40 to 48 Gy to the gross metastatic lesion, and as 30 to 42 Gy to a 5-mm margin to the metastatic lesion. Double-dose gadolinium contrast-enhanced magnetic resonance imaging at 1-mm slice thickness was performed before treatment and at 1, 4, and 7 months post-treatment. The tumor volume reduction ratio was calculated for each follow-up. Between July 2011 and September 2012, 11 patients with 70 lesions were included in this analysis. The median number of lesions per patient was 4 (range, 2-15). The median initial tumor volume was 0.235 cm³ (range, 0.020-10.140 cm³). The treatment plans were evaluated regarding conformation number (CN), target coverage (TC), and homogeneity index (HI). The median follow-up duration was 14 months (range, 3-25 months) and the 1-year intracranial control rate was 67%. The tumor volume reduction was most prominent during the first month with a median reduction rate of 0.717 (range, −0.190 to 1.000). Complete remission was seen in 22 (33%) lesions, and 45 (64%) lesions showed more than 65% reduction in tumor volume. The CN, TC, and HI values were comparable to that of previous studies, and the mean hippocampal dose was 13.65 Gy. No treatment breaks or ≥G3 acute toxicities were observed during or after treatment. The HS-WBRT with SIB in patients with multiple brain metastases was effective and feasible for volume reduction and showed excellent intracranial control.