The paramedian forehead flap provides excellent aesthetic and functional results for the reconstruction of full-thickness maxillary defects. However, previous radiation therapy reduces elasticity of tissues and their healing capacity. We describe the use of Lyoplant, an absorbable biocompatible membrane derived from bovine pericardium, for full-thickness maxillary reconstruction after maxillectomy in an irradiated patient, providing a step-by-step description of the procedure. The Lyoplant membrane was sutured to the internal edge of the refreshed borders of the maxillary defect, to achieve a complete closure of the loss of sinonasal mucous membrane and to guarantee a support to the forehead flap. It can drive sinonasal mucosa regeneration with early resolution of nasal crusting. No complications, such as infection, extrusion, or subsidence of the flap, were observed. Lyoplant can be considered a safe and easily available support for locoregional flap and mucosa regeneration in post-operative defects of nasal cavity and central face in irradiated patients.