Bromodomain-containing protein 4 (BRD4) binds acetylated lysine residues on histones to facilitate the epigenetic regulation of many genes, and it plays a key role in many cancer types. Despite many prior reports that have explored the importance of BRD4 in oncogenesis and the regulation of epigenetic memory, its role in esophageal squamous cell carcinoma (ESCC) progression is poorly understood. Here, we investigated BRD4 expression in human ESCC tissues to understand how it regulates the biology of these tumor cells. BRD4 expression in ESCC tissues was measured via immunohistochemical staining. BRD4 inhibition in the Eca-109 and KYSE-150 ESCC cell lines was conducted to explore its functional role in these tumor cells. BRD4 overexpression was observed in ESCC tissues and cells, and inhibiting the function of the gene impaired the proliferative, invasive, and migratory activity of these cells while promoting their apoptosis. Cyclin D1 and c-Myc expression were also suppressed by BRD4 inhibition, and the expression of key epithelial-mesenchymal transition markers including E-cadherin and Vimentin was markedly altered by such inhibition. BRD4 plays key functional roles in the biology of ESCC, proposing that it could be a viable therapeutic target for treating this cancer type. [ABSTRACT FROM AUTHOR]