Background: Metastasis to regional lymph nodes represents the first step of dissemination in esophageal cancer and serves as an unfavorable prognostic indicator for disease progression. The formation of tumor lymphatic microvessels is dependent on the production of lymphangiogenic growth factors by tumor cells, such as vascular endothelial growth factor C (VEGF-C), metastasis-associated gene 1 (MTA1), and hypoxia inducible-factor l alpha (HIF-1 alpha). The degree of intratumoral lymphatic microvessel density (LMVD) by immunohistochemistry is thought to influence tumor lymph node metastasis (LNM) and prognosis in various solid tumors. The aim of this study was to investigate the expression of MTA1 and HIF-1a in human esophageal cancer and to explore the relationship between their expression and lymphangiogenesis. Method: The expression of MTA1 and HIF-1a, and LMVD marked by D2-40 were detected using immunohistochemical staining in eighty-two human esophageal cancer cases. Results: The positive rates of MTA1 and HIF-1a expression were 69.5% and 59.8%, respectively. The expression of MTA1 and HIF-1a were both correlated with LNM. In addition, MTA1 and HIF-1a expression has a positive correlation in human esophageal cancer; LMVD correlated significantly with LNM. LMVD in MTA1 and HIF-1a over-expression cases was higher than that in none or weak cases, and this difference has statistical significance. Conclusion: Our findings suggest that MTA1 plays an important role in lymphangiogenesis and LNM by stabilizing HIF-1a in esophageal cancer. The inhibition of lymphangiogenesis, MTA1, or HIF-1a activity may have an important therapeutic benefit in the control of esophageal cancer.