Abstract: Echinoside A (EA), a triterpene glycoside, was obtained from the sea cucumber Pearsonothuria graeffei, which is rich with triterpene glycoside. The effects and mechanism of EA on tumor metastasis were conducted. MTT assay was used to determine the anti-proliferation ability of EA on HepG2 tumor cells and human umbilical vein endothelial cells (HUVEC). Cell adhesion assay, wound migration assay and transwell assay were used to determine the effects of EA on tumor cell adhesion, migration, invasion abilities. In vitro tube formation assay and chicken embryo chorioallantoic membrane (CAM) assay were used to determine the effects of EA on tumor angiogenesis. In this study, we found that EA inhibited the proliferation of HepG2 and HUVEC cells, and suppressed HepG2 cell adhesion, migration, and invasion in a dose-dependent manner. EA also obviously reduced tube formation of HUVEC cells on matrigel in vitro and attenuated neovascularization in the CAM assay in vivo. Immunocytochemical analysis and western blotting analysis revealed that EA significantly decreased the expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF). EA also increased the expression level of tissue inhibitor of metalloproteinase-1 (TIMP-1). Meanwhile, the expression of nuclear factor-kappa B p65 (NF-κB p65) was not affected by EA. These findings suggest that EA exhibits significant anti-metastatic activity through specific inhibition of MMP-9 signal pathway.