The Aurora-A gene encodes a serine/threonine protein kinase that is frequently overexpressed in several types of human tumors. The overexpression of Aurora-A has been observed to associate with the grades of differentiation, invasive capability and distant lymph node metastasis of esophageal squamous cell carcinoma (ESCC). However, the molecular mechanism by which Aurora-A promotes malignant development of ESCC is still largely unknown. In this study, we show that Aurora-A overexpression enhances tumor cell invasion and metastatic potential in vitro and in vivo. Furthermore, Aurora-A overexpression inhibits the degradation of β-catenin, promotes its dissociation from cell–cell contacts and increases its nuclear translocation. We also demonstrate for the first time that Aurora-A directly interacts with β-catenin and phosphorylates β-catenin at Ser552 and Ser675. Substitutions of serine residue with alanine at single or both positions substantially attenuate Aurora-A-mediated stabilization of β-catenin, abolish its cytosolic and nuclear localization as well as transcriptional activity. In addition, Aurora-A overexpression is significantly correlated with increased cytoplasmic β-catenin expression in ESCC tissues. In view of our results, we propose that Aurora-A-mediated phosphorylation of β-catenin is a novel mechanism of malignancy development of tumor.