BACKGROUND To identify predictors for health-related quality of life (HRQOL) in survivors of childhood brain tumors and its relationship to cognitive function. METHODS One hundred twenty-six consecutive Danish childhood brain tumor patients treated 1970-1997 and being 7.9-40.4 years at follow-up were assessed for general intelligence (IQ) and administered the Minneapolis-Manchester Quality of Life (MMQL) questionnaire. RESULTS In multivariate linear regression treatment with RT was the most important risk factor for reduced HRQOL. Lower scores for physical functioning and energy, social functioning, cognitive functioning, body image, outlook of life, and intimate relations were significantly related to RT. Tumor location in the posterior fossa was associated with lower scores for physical functioning and energy, and tumor site in the third ventricle region was associated with lower scores for body image. Younger age at diagnosis was associated with lower scores for social functioning and intimate relations, and younger age at follow-up was associated with more physical symptoms. When IQ was included as a covariate, RT only remained significant for social functioning and intimate relations while tumor location in the third ventricle region remained significant for body image, younger age at diagnosis for social functioning and intimate relations, and younger age at follow-up for physical symptoms. In contrasts, neither gender nor presence of hydrocephalus requiring shunt inserted predicted significantly reduced HRQOL in the multivariate analyses. CONCLUSIONS RT is an important predictor of HRQOL primarily due to its effect on general intelligence, which suggests that IQ is a strong determinant of HRQOL.