Curcumin, a biphenyl compound derived from rhizome, is a powerful anti-cancer agent. Emodin is an active component isolated from the root and rhizome of Rheum palmatum that has been widely used in traditional Chinese medicine for the treatment of various diseases. Currently, there are no studies examining the effect of curcumin in combination with emodin on tumor cell growth. In this study, we report for the first time that combined curcumin and emodin administration synergistically inhibits proliferation (MTT assay), survival (flow cytometry), and invasion (transwell migration assay) of breast cancer cells. Synergism is determined by the Chou-Talalay method. Moreover, we demonstrate that miR-34a is upregulated by curcumin and emodin. This microRNA helps mediate the anti-tumor effects of curcumin and emodin by downregulating Bcl-2 and Bmi-1. Our results not only provide insight into the mechanism of synergy between curcumin and emodin in breast cancer cells, but also suggest a new and potentially useful approach for breast cancer therapy.