Objectives: To assess the independent prognostic value of standardized uptake value (SUV) and apparent diffusion coefficient (ADC), separately and combined, in order to evaluate if the combination of these two variables allows further prognostic stratification of patients with head and neck squamous cell carcinomas (HNSCC). Methods: Pretreatment SUV and ADC were calculated in 57 patients with HNSCC. Mean follow-up was 21.3 months. Semiquantitative analysis of primary tumours was performed using SUVmaxT/B, ADCmean, ADCmin and ADCmax. The prognostic value of SUVmaxT/B, ADCmean, ADCmin and ADCmax in predicting disease-free survival (DFS) was evaluated with log-rank test and Cox regression models. Results: Patients with SUVmaxT/B ≥5.75 had an overall worse prognosis (p = 0.003). After adjusting for lymph node status and diameter, SUVmaxT/B and ADCmin were both significant predictors of DFS with hazard ratio (HR) = 10.37 (95 % CI 1.22–87.95) and 3.26 (95 % CI 1.20–8.85) for SUVmaxT/B ≥5.75 and ADCmin ≥0.58 × 10−3 mm2/s, respectively. When the analysis was restricted to subjects with SUVmaxT/B ≥5.75, high ADCmin significantly predicted a worse prognosis, with adjusted HR = 3.11 (95 % CI 1.13–8.55). Conclusions: The combination of SUVmaxT/B and ADCmin improves the prognostic role of the two separate parameters; patients with high SUVmaxT/B and high ADCmin are associated with a poor prognosis. Key Points: • High SUVmaxT/Bis a poor prognostic factor in HNSCC • High ADCminis a poor prognostic factor in HNSCC • In patients with high SUVmaxT/B, high ADCminidentified those with worse prognosis