Background: The aim of the present trial is to investigate a new option of skin protection in order to reduce the rate of grade≥2 skin toxicity in patients receiving radiotherapy alone or radiochemotherapy for locally advanced squamous cell carcinoma of the head-and-neck (SCCHN). Methods / Design: This is a randomized, active-controlled, parallel-group multi-center trial that compares the following treatments of radiation dermatitis in patients with head-and-neck cancer: Mepitel® Film (Arm A) vs. standard care (Arm B). The primary aim of this trial is to investigate the rate of patients experiencing grade≥2 radiation dermatitis (according to Common Toxicity Criteria for Adverse Events (CTCAE) Version 4.03) until 50Gy of radiotherapy. Evaluation until 50Gy of radiotherapy has been selected as the primary endpoint, since up to 50Gy, the irradiated volume includes the primary tumor and the bilateral cervical and supraclavicular lymph nodes, and, therefore, is similar in all patients. After 50Gy, irradiated volumes are very individual, depending on location and size of the primary tumor, involvement of lymph nodes, and the treatment approach (definitive vs. adjuvant). In addition, the following endpoints will be evaluated: Time to grade 2 radiation dermatitis until 50Gy of radiotherapy, rate of patients experiencing grade≥2 radiation dermatitis during radio(chemo)therapy, rate of patients experiencing grade≥3 skin toxicity during radio(chemo)therapy, adverse events, quality of life, and dermatitis-related pain. Administration of Mepitel® Film will be considered to be clinically relevant, if the rate of grade≥2 radiation dermatitis can be reduced from 85% to 65%. Discussion: If administration of Mepitel® Film instead of standard care will be able to significantly reduce the rate of grade≥2 radiation dermatitis, it could become the new standard of skin care in patients irradiated for SCCHN.