Objectives: This study aimed to examine the relationship between health-related quality of life (HRQoL) and sociodemographic and clinical variables in survivors of head and neck cancer (HNC) treated with radiotherapy, with or without surgery. Materials and Methods: HRQoL was measured using the functional assessment of cancer therapy—head and neck (FACT-H&N) in a cross-sectional survey involving 150 patients. Of these, 60 had nasopharyngeal cancer (NPC), treated exclusively with radiotherapy, while 90 had oral cavity squamous cell cancer (OSCC), undergoing radical surgery followed by adjuvant radiotherapy. Key variables included cancer type, age, gender, partnership status, education, and employment, with additional clinical variables assessed in patients with OSCC. Statistical analyses included multiple regression, ANOVA, and t-tests to explore relationships between variables and HRQoL. Results: Cancer type, surgical treatment, and employment status emerged as significant independent predictors of HRQoL in HNC patients. Patients with NPC reported better HRQoL on three FACT-H&N subscales—social/family well-being, functional well-being, and additional concerns—compared to patients with OSCC. Unemployed individuals exhibited lower HRQoL on four subscales. In patients with OSCC, partnership status and segmental mandibulectomy were found to predict HRQoL independently. Conclusions: This study concludes that cancer type, surgical intervention, and employment status notably influence HRQoL among HNC patients undergoing radiotherapy. In addition, partnership status is a key factor affecting HRQoL in patients with OSCC.