Hedyotis diffusa has been used to treat cancers in traditional Chinese medicine for many years. Recently, sev-eral anthraquinone compounds were extracted from Hedyotis diffusa and identified as its anticancer ingredients. These compounds are able to induce apoptosis in several types of cancer cells. In this study, we showed that the anticancer activ-ity of Hedyotis diffusa was highly selective, possessing high cytotoxicity towards human breast cancer MCF7 cells but almost no cytotoxicity against the mammary epithelial MCF12A cells. The Hedyotis diffusa water extract also elevated the energy metabolism in both MCF12A and MCF7 cells; but the ATP/ADP ratio was still maintained at about 1.0 in the MCF12A cells to avoid either apoptosis or uncontrolled proliferation. In addition, Sheshecaojing, a health product of He-dyotis diffusa marketed in China, gave a dose-dependent cytotoxic response against the MCF7 cells.