Background. Patients with head and neck squamous cell carcinoma (HNSCC) often lose a considerable amount of muscle mass following the disease and treatment. This is an independent mortality predictor, lowering muscle strength and functional performance. Progressive resistance training (PRT) increases muscle mass among healthy individuals and groups of cancer patients, but it has not been investigated in HNSCC patients. Furthermore, studies in healthy subjects show an additive effect of protein and creatine supplementation following PRT. Objectives. Firstly, to investigate the feasibility of 12 weeks of PRT ± protein and creatine supplementation among HNSCC patients. Secondly, to investigate group changes over time and group differences regarding lean body mass (LBM), muscle strength and functional performance following PRT ± dietary supplementation. Material and methods. Thirty patients were randomized into two groups: a PROCR group undergoing a seven-day pre-trial creatine loading protocol followed by 12 weeks of PRT with creatine and protein supplementation and a PLA group undergoing a seven-day pre-trial placebo ingestion protocol followed by an identical PRT protocol with placebo supplementation. Before the pre-trial and pre- and post-PRT evaluation of LBM, maximal isometric and isokinetic muscle strength and functional performance were performed. Results. Seventy percent of the patients completed the intervention and the PRT adherence rate was 97%. No significant group differences were found in any endpoints. From pre- to post-PRT, LBM increased significantly in the PROCR group by 2.6 ± 2.2 kg (p < 0.0001) and increased in the PLA group (1.3 ± 1.1 kg, p = 0.07). Maximal isometric and isokinetic muscle strength as well as functional performance increased significantly in both groups. Conclusion. PRT is feasible in radiotherapy treated HNSCC patients. Following PRT, lean body mass, muscle strength and functional performance increased significantly in both groups (LBM only borderline significant in PLA group) with no significant group difference in any endpoint.