Collectively, these data indicated that HIC1 has a direct suppression on cell proliferation, migration, invasion and EMT of ESCC cells through the inhibition of EphA2 signaling pathway, consistent with our clinical findings that HIC1 expression level was negatively correlated with the malignancy and metastasis of ESCC cells. The gene discussed is HIC1; the disease is esophageal squamous cell carcinoma.