Results showed that both HIC1 hypermethylation and HIC1 downregulation both at mRNA and protein level were significantly correlated with vascular invasion, lymph node metastasis and clinical stage, respectively (all P < 0.05), suggesting that frequent dysfunction of HIC1 through its promoter methylation might play crucial roles in malignant progression of human esophageal cancer and might have a important impact on the metastasis and poor survival of ESCC patients. The gene discussed is HIC1; the disease is esophageal cancer.