Abstract Background Quality of life (QoL) is influenced in head and neck cancer (HNC) patients by a set of factors related to diagnosis, treatment and tumor impacts. The aim of this study was to evaluate the Quality of Life (QoL) changes in Head and Neck cancer (HNC) patients during treatment (radiotherapy and/or chemoradiotherapy). Methods QoL was evaluated prospectively in 63 HNC patients during radiotherapy and/or chemoradiotherapy at three moments: before or at beginning (T0), in the middle (T1 ~ four weeks) and immediately at the end (T2 ~ eight weeks) of treatment. The differences between the scores at different time points was verified using Friedman’s non-parametric test. Negative changes between time points were evaluated, with differences (delta) of ±10 points being considered to be clinically significant. Results The total mean age was 59.1 ± 9.5y, and 82.5% were male. The oral cavity and larynx were more frequent tumors. The functional score for ‘role’ was decreased at time points T1 and T2 as compared to T0, while an improvement in scores was observed for cognitive function. Several physical symptoms also worsened over time, such as: fatigue, nausea and vomiting, dry mouth and sticky saliva, swallowing and skin symptoms, senses and teeth problems. A high frequency of altered and clinically meaningful values were observed for most of domains, ranging from 6 to 74%. Conclusions The QoL became worse at approximately one month after treatment beginning in HNC patients, and this remained until the end of therapy. Protocols directing to early nutritional counseling and management of symptoms of nutritional impact are important to improve clinical outcomes. This is part of preventive actions aiming to make the exhausting treatment process less traumatic and easier to complete.