Fatty acid synthase (FAS) has attracted more and more attention as a potential target for cancer treatment. Natural FAS inhibitors are emerging as potential therapeutic agents to treat cancer. Rheum tanguticum Maxim. ex Balf. (rhubarb) is a traditional Chinese nutritional food and has been reported to possess a variety of biological activities, including the ability to induce the apoptosis of cancer cells. This study indicates that desoxyrhaponticin (DC) and rhaponticin (RC), two stilbene glycosides from rhubarb, could be considered as promising FAS inhibitors. We found that both DC and RC could inhibit intracellular FAS activity and downregulate FAS expression in human breast cancer MCF-7 cells. In addition, the apoptotic effect of DC on human cancer cells was announced for the first time. Since FAS plays a key role in the biosynthesis pathway of fatty acids in cancer cells, these findings suggest that DC has potential applications in the prevention and treatment of cancer.