The purpose of the present study is to determine the impact of illness characteristics and psychopathological comorbidity on the quality of life (QoL) of radio-oncological patients in health-related and individual dimensions. Sixty-three of 93 eligible patients (40 women and 23 men) were included in the study during their radiation therapy visit to an outpatient centre annexed to a community hospital in Southern Bavaria, Germany. In a semi-structured interview, we elicited individually relevant life domains rated by the patients according to the ‘Schedule for the Evaluation of Individual Quality of Life – Direct Weighting’. In addition, the participants completed the ‘European Organization for Research and Treatment of Cancer (EORTC) QoL Questionnaire Core 30’ and the ‘Hospital Anxiety and Depression Scale’. We also assessed the demand for psychotherapy and utilization of psycho-oncological services. In total, 9.5% of the examined patients suffer from clinically relevant anxiety and/or depression [total Hospital Anxiety and Depression Scale (HADS) score >19]. There was a weak positive correlation between Karnofsky’s Performance Status and QoL. Anxiety and depression were significantly correlated with impaired QoL, especially with impaired individual QoL. There was no association between psychopathological comorbidity and the requirement for psycho-oncological support. Conversely, patients who report difficulties in accepting help had a significantly lower QoL. Psychopathological comorbidity has a considerable influence on QoL of patients undergoing radiotherapy. Measuring the individual QoL appears as an adapted needs assessment and helps the psychotherapist in focusing on the patient’s problems and desires. Furthermore, the patient’s QoL is a main target in providing or planning mental health care in non-university oncological services.