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Background: Inflammatory disease of upper airway in pediatric population represents a social problem for both the pharmaco-economic impact and a burden for the family. To date, the use of topical therapies represents a significant therapeutic progress because they are able to reduce mucosal inflammation and improve tissue healing. Topical Hyaluronic Acid (HA) is a promising molecule that has been recently proposed as adjuvant treatment in the inflammatory disease of the upper aerodigestive tract (UADT) infections. Aims: The aim of our work was to review the published literature regarding all the potential therapeutic effects of HA in the inflammatory disease of upper airway in pediatric population and evaluate the effectiveness of HA, alone or in combination, in children affected by cystic fibrosis. Methods: Relevant published studies about use of HA in UADT in pediatrics were searched in Pubmed, Google Scholar, Ovid using various keywords with no limit for the year of publication. Studies based on the use of HA with nasal packing and with invasive administration of HA were excluded. Results: At the end of our selection process, four publications have been included: one of them in children with recurrent upper respiratory tract infections, one of them in children with bacterial acute rhinopharyngitis, two of them in children affected by cystic fibrosis. Conclusions: Topical administration of HA plays a pivotal role in all the children suffering from UADT inflammatory disease, and positive results are generally observed in children with cystic fibrosis.