BACKGROUND: We sought to construct the optimal neurocognitive function (NCF) change criteria sensitive to health-related quality of life (HR-QOL) in patients who have undergone whole-brain radiation therapy (WBRT) for brain metastasis. METHODS: We categorized the patients by the changes of NCF into groups of improvement versus deterioration if at least one domain showed changes that exceeded the cut-off while other domains remained stable. The remaining patients were categorized as stable, and the patients who showed both significant improvement and deterioration were categorized as 'both.' We examined the clinical meaning of NCF changes using the cut-off values 1.0, 1.5, and 2.0 SD based on the percentage of patients whose HR-QOL changes were ≥ 10 points. RESULTS: Baseline, 4-month and 8-month data were available in 78, 41 (compliance; 85%), and 29 (81%) patients, respectively. At 4 months, improvement/stable/deterioration/both was seen in 15%/12%/41%/32% of the patients when 1.0 SD was used; 19%/22%/37%/22% with 1.5 SD, and 17%/37%/37%/9% with 2.0 SD. The HR-QOL scores on the QLQ-C30 functional scale were significantly worse in the deterioration group versus the others with 1.0 SD (p = 0.013) and 1.5 SD (p = 0.015). With 1.5 SD, the HR-QOL scores on the QLQ-BN20 was significantly better in the improvement group versus the others (p = 0.033). However, when 'both' was included in 'improvement' or 'deterioration,' no significant difference in HR-QOL was detected. CONCLUSIONS: The NCF cut-off of 1.5 SD and the exclusion of 'both' patients from the 'deterioration' and 'improvement' groups best reflects HR-QOL changes.