NDRG1 has been reported to exert pivotal roles in tumor progression and metastasis via Wnt/β-catenin signal. However, as the same subfamily of NDRG1, little is known about the role of NDRG3 in the hepatocarcinogenesis. The present study was aimed to characterize the expression pattern and understand its biological roles in hepatocarcinogenesis, as a means to exploit it for therapeutic purposes. In this study, we revealed that NDRG3 was up-regulated in HCC tissues and higher NDRG3 expression was associated with significantly shorter overall survival. What’s more, lower NDRG3 was found to be markedly positive correlation with metastasis-free survival. In vitro and in vivo experiments revealed that knock-down of NDRG3 inhibits HCC metastasis and angiogenesis. We further demonstrated that Activation of WNT/β-catenin signaling and enhanced CSC-like properties was responsible for the NDRG3-mediated promoting effect on HCC. In conclusion, the principal findings demonstrated that high NDRG3 expression facilitates HCC metastasis via regulating the turnover of β-catenin, as well as provides a potential therapeutic target for future therapeutic interventions.