Head and neck squamous-cell carcinoma (HN-SCC) patient management is mainly based on TNM classification and needs be improved by considering other potentially useful prognostic factors. We examined the pre-radiotherapy tumor potential doubling time (Tpot) evaluated after in vivo infusion of bromodeoxyuridine and flow-cytometric analysis and the early clinical tumor regression after 40 Gy (40 Gy-TR). Tpot values and clinical 40 Gy-TR classes (minor and major) were available for 82 HN-SCC patients. Radiation therapy completion was done either with 1 dose per day (conventional regimen) or 2 doses per day (accelerated regimen). Local control was also available for follow-up times above 4 years. We found that major 40 Gy-TR was strongly correlated with fast tumor growth, characterized by Tpot values below 5 days, and that patients with major 40 Gy-TR showed better local control than those with minor 40 Gy-TR, independently from the radiotherapy regimen type. We also found that treatment completion with accelerated radiotherapy gave better local control for patients with major 40 Gy-TR and fast tumor growth than conventional radiotherapy. Multivariate analysis, performed on all patients, assigned an independent prognostic value to Tpot, tumor classification and 40 Gy-TR.