Trigonella foenum in graecum (Fenugreek) is a traditional herbal plant used to treat disorders like diabetes,high cholesterol, wounds, inflammation, gastrointestinal ailments, and it is believed to have anti-tumor properties,although the mechanisms for the activity remain to be elucidated. In this study, we prepared a methanol extractfrom Fenugreek whole plants and investigated the mechanism involved in its growth-inhibitory effect on MCF-7 human breast cancer cells. Apoptosis of MCF-7 cells was evidenced by investigating trypan blue exclusion,TUNEL and Caspase 3, 8, 9, p53, FADD, Bax and Bak by real-time PCR assays inducing activities, in thepresence of FME at 65 μg/mL for 24 and 48 hours. FME induced apoptosis was mediated by the death receptorpathway as demonstrated by the increased level of Fas receptor expression after FME treatment. However,such change was found to be absent in Caspase 3, 8, 9, p53, FADD, Bax and Bak, which was confirmed by atime-dependent and dose-dependent manner. In summary, these data demonstrate that at least 90% of FMEinduced apoptosis in breast cell is mediated by Fas receptor-independently of either FADD, Caspase 8 or 3, aswell as p53 interdependently.