© 2021 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-FacialIntroduction: Gelsolin protein has important cellular functions, including cell motility and apoptosis. Altered gelsolin expression has been reported in several types of neoplasms, but clinicopathological features of gelsolin are currently unclear in patients with laryngeal squamous cell carcinoma. Objectives: Our aim is to investigate the clinicopathological significance of gelsolin as a prognostic biomarker for laryngeal squamous cell carcinoma. Methods: Tissue specimens from 168 patients with laryngeal squamous cell carcinoma were immunohistochemically assessed for the Gelsolin expression. Prognostic significance of Gelsolin and its interaction with clinical parameters was analysed. Results: Gelsolin expression was confirmed in 70.2% of cases. Gelsolin expression is significantly associated with tumor stage, tumor grade, and locoregional recurrence. Kaplan–Meier survival curves revealed that Gelsolin expression inversely correlated with both disease-specific and overall survival. Conclusion: This research is the first to demonstrate that Gelsolin expression is associated with a poor prognosis in laryngeal squamous cell carcinoma. Gelsolin is a novel promising biomarker and attractive target for the treatment of laryngeal squamous cell carcinoma.