Hypopharyngeal squamous cell carcinoma (HPSCC) is a common malignant tumor of the head and neck, characterized by a high degree of malignancy and significantly poor outcome. Charged multivesicular body protein 4 C (CHMP4C) is an important subunit of the Endosomal Sorting Complex Required for Transport-III (ESCRT-III), which is mainly involved in cytokinetic abscission. Moreover, CHMP4C plays an important role in cancer development. However, the mechanism of CHMP4C's role in hypopharyngeal squamous cell carcinoma is unclear. Therefore, the aim of this study was to investigate the biological role and potential mechanism of CHMP4C in hypopharyngeal squamous cell carcinoma. First, we evaluated the expression of CHMP4C in hypopharyngeal squamous cell carcinoma tissues and normal tissues using HPA database. Knockdown of CHMP4C in cell lines was achieved using lentivirus, and the effects of CHMP4C on cell proliferation were detected by CCK-8 and cell colony formation assay; cell migration and invasion abilities were assessed by Transwell assay; cell cycle distribution and apoptosis levels were detected by flow cytometry. Finally, the expression of the epithelial-mesenchymal transition (EMT)-related proteins and the Wnt/β-catenin signaling pathway-related proteins was investigated using Western blot. The results revealed that CHMP4C expression was upregulated in hypopharyngeal squamous cell carcinoma tissues compared with normal tissues. Knockdown of CHMP4C inhibited Fadu cell proliferation, migration, and invasion. Knockdown of CHMP4C could promote apoptosis by blocking the S-phase of the cell cycle. In addition, we found that knockdown of CHMP4C resulted in upregulation of E-cadherin protein expression and downregulation of N-cadherin and Vimentin protein expression; meanwhile, knockdown of CHMP4C resulted in the downregulation of β-catenin and C-myc protein expression, suggesting that CHMP4C is involved in the Wnt/β-catenin signaling pathway. CHMP4C may promote the progression of hypopharyngeal squamous cell carcinoma through the Wnt/β-catenin signaling pathway. CHMP4C is a very promising target for tumor therapy.© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.