Hypoxia inducible factor 1α (HIF-1α) is highly expressed and is implicated in the progression of esophageal squamous cell carcinoma. To investigate the potential mechanism by which HIF-1α contributes to the progression of esophageal squamous cell carcinoma, here we established stable esophageal carcinoma cell lines Eca-109 and TE- 13 in which HIF-1α was depleted by shRNA mediated gene silencing. In additon, we used specific inhibitor YC-1 to inhibit HIF-1α expression. Our in vitro studies demonstrated that shRNA or chemical mediated inhibition of HIF-1α led to reduced proliferation and increased apoptosis of esophageal carcinoma cells, as well as the downregulatuion of HIF-1α targets VEGF, MMP2 and BCL2. Furthermore, we employed xenograft nude mice model to validate the in vitro findings and proved that depletion of HIF-1α suppressed the tumorigenicity of esophageal carcinoma cells in vivo. In conclusion, our results provide new insight into the potential role of HIF-1α in esophageal squamous cell carcinoma and open up the possibility of inhibiting HIF-1α for targeted therapy of esophageal squamous cell carcinoma.