The aim of this study was to determine the effect of A disintegrin and metalloprotease 10 (ADAM10) protein expression on the progression, migration and prognosis of hypopharyngeal squamous cell carcinoma (HSCC). Immunohistochemistry and western blot analysis were performed to detect ADAM10 expression in human HSCC specimens. Cell Counting Kit-8 (CCK-8) assay, flow cytometry analysis and wound-healing assay were employed to investigate the effects of ADAM10 knockdown (ADAM10-RNAi) on major oncogenic properties of FaDu cells. We detected that ADAM10 was overexpressed in HSCC specimens and its expression level was associated with differentiation (p<0.001), tumor size (p=0.019), lymph node metastasis (p=0.001), clinical stage (p<0.001), proliferation marker Ki-67 expression (P=0.001) and overall survival (p<0.046). ADAM10-RNAi in FaDu cells resulted in the inhibition of proliferation and the decrease in migration. Moreover, mechanistic experiments revealed that ADAM10-RNAi resulted in an increase in E-cadherin and a decrease in N-cadherin and vimentin expression. Our study implies that high expression of ADAM10 promotes the proliferation and migration of HSCC. These findings may help to provide a method for treatment of HSCC.