Several approaches have been proposed for soft tissue augmentation using injectable materials for lip and soft-tissue augmentation due to their physical and biological properties. Hyaluronic acid represents a natural component of the connective tissues, related to wound healing and skin regeneration. The aim of this research was to investigate the clinical and histological effectiveness of cross-linked hyaluronic acid for lip augmentation. A total of 8 patients were treated for lip augmentation with a clinical follow up of 60 days. After this period a histological evaluation was performed to evaluate the healing of the treated regions. The healing phase reported no inflammatory response, tissue contractions and no local flogistic evidence in the treated areas, where the filling volume appeared maintained. The 60 days histological evaluation showed evidence of filler resorption with few infiltrated inflammatory cells. The clinical and histological findings suggested that cross-linked hyaluronic acid represents a safe and effective tool for lip augmentation.