Radiotherapy is a commonly applied treatment modality for head and neck malignancies. Despite its proven effectiveness in improving cure rates, it is associated with several complex oral complications that may confound treatment planning for prosthetic rehabilitation. The most common intraoral adverse effects include xerostomia, mucositis, dental caries and osteoradionecrosis. Prosthetic rehabilitation with removable dentures in irradiated patients presents specific clinical challenges. These difficulties result from tissue fragility, chronic limitation of mouth opening, reduced salivary flow, increased susceptibility to fungal infections, and the persistent risk of osteoradionecrosis. Such conditions complicate prosthetic management and require the application of specific precautionary measures, particularly in the area of removable prosthodontics. The aim of this paper is to present, through a clinical case, the specific characteristics and precautionary measures required at the various stages of fabrication of a complete removable prosthesis in an edentulous patient who underwent irradiation of the oro-facial region.