In this study, we find for the first time that HDAC4 mRNA and protein are overexpressed in ESCC tissues compared with matched normal esophageal tissues, and high mRNA level is associated with low differentiation (high pathological grade), lymph node metastasis, large or invasive tumor and advanced TNM stage in ESCC patients. This evidence concerns the gene HDAC4 and esophageal squamous cell carcinoma.