Many natural products have been shown to have inhibitory effects on the metastatic process of various cancers including breast cancer. An active triterpenoid saponin D Rhamnose β-hederin (DRβ-H) from Clematis ganpiniana, has been known induce the apoptosis of breast cancer cells, but the effect of DRβ-H on the metastasis of breast cancer cells is largely unknown. In this study, we demonstrated that a non-cytotoxic concentration of DRβ-H markedly suppressed wound healing migration, migration through the chamber and invasion through the matrigel. In addition, DRβ-H regulated expression of RNPC1, E-cadherin proteins of MDA-MB-231 cells. Furthermore, RNPC1 knockdown decreased the DRβ-H-induced up-regulation of RNPC1 and E-Cadherin in MDA-MB-231 cells. RNPC1 knockdown reduced the anti-metastasis activities of DRβ-H, meaning that the up-rugulation of RNPC1 by DRβ-H is essential for its anti-metastatis activities. These results suggest that DRβ-H might be a potential therapeutic candidate for the treatment of breast cancer metastasis.