Factors affecting the quality of life (QOL) in patients undergoing radiation therapy for head and neck cancer were determined in a prospective study. Full psychiatric interviews and self-report questionnaires concerning patients' QOL, pain, anxiety, mood, coping style and personality were administered to 35 patients with Stage I or II head and neck cancer before radiation therapy (week 0), and approximately one month (week 4) and two months (week 8) after starting of radiation. Anxiety, depression and pain were more severe at week 4 than at baseline. Anxiety was less at week 8, but depressive symptoms remained remarkable. Stepwise regression analyses revealed that changes in depressed mood and pain partially accounted for changes in disease-specific QOL. General health QOL related to a premorbid personality of openness and an emotional aspect of a coping style. Therapeutic interventions including psychiatric management of depression and physical management of pain appear to be crucial for preserving QOL during radiation treatment of patients with head and neck cancer. Copyright © 2005 John Wiley & Sons, Ltd.