The objective of this study is to provide a content comparison of frequently used questionnaires that assess health-related quality of life (hrQOL) in head and neck cancer (HNC) survivors. This systematic content comparison describes which specific areas of hr-QOL research are covered by each questionnaire. Thereby, it shall assist the clinician in the decision process of instrument selection depending on the content of the study question. As a reference, we chose the international classification of functioning, disability and health (ICF), which was adopted by the WHO in 2001. A systematic literature review identified current hrQOL questionnaires relevant for HNC. The concepts of functioning contained in each questionnaire were translated (linked”) to the ICF according to standardized guidelines. Nine questionnaires were selected for further analyses: EORTC-QLQ (C30 + HN35), FACT (G + HN), UW_QOL, QOL-RTI, HN-QOL, PSS-HN, VHI, LORQ, XQ. Within the selected questionnaires, there are 474 concepts, matching 74 second-level ICF categories. The results are presented in tables, showing for each of the validated questionnaires, which of these 74 categories of functioning are addressed. In terms of diversification of content among the questionnaires, there are just eight categories that are used rather frequently and apply to at least five (out of nine) of the questionnaires: e110 Products for personal consumption (i.e., food, drugs), b510 ingestion function, b152 emotional function, b280 sensation of pain, b310 voice, d550 eating, b130 energy and drive function and d850 employment. This ICF-based content comparison provides detailed information on the content that is covered in each questionnaire and thereby assists questionnaire selection. The results question the assumption that HNC-specific questionnaires generally cover the same content. Depending on the study question, the population to be studied and the intervention, there is no unique ideal questionnaire. Compared with other types of qualitative review, the most important advantage of content comparison based on the ICF is the use of an external and independent reference.