BACKGROUND: Head and neck cancer (HNC) patients experience a variety of post-treatment symptoms that affect their quality of life (QoL). This study aims to assess the most prevalent symptoms and their relationship to cancer stage (UICC I-IV) while identifying areas for targeted intervention. METHODS: A cross-sectional study was conducted involving 340 HNC patients at the University Hospital Erlangen from January to December 2019. QoL and its domains were assessed using the German version of the University of Washington Quality of Life Questionnaire Version 4 (UW-QoL v.4), with comparisons made between early-stage (UICC I & II, n = 180) and advanced-stage (UICC III & IV, n = 160) patients. Statistical analysis examined differences in QoL and its individual domains. RESULTS: Advanced-stage patients reported significantly greater impairments in several QoL domains, including swallowing (p = 0.003, η CONCLUSION: Advanced-stage HNC patients experience a significantly higher burden of physical symptoms, particularly issues with swallowing, saliva, and taste, necessitating early and targeted interventions. Psychological issues are also prevalent and should be addressed in both early- and advanced-stage patients. Despite non-significant differences in some symptoms, their clinical relevance may still be important, particularly in individual cases. Comprehensive care, including physical and emotional support, is essential to improving long-term QoL for HNC patients. Further research should focus on longitudinal assessments and clinically meaningful thresholds for symptom management.