Medicinal values of mulberry are known to humans from ancient ages. The white mulberry, Morus alba L. is a rich source of many bioactive phytochemicals. Earlier investigations in our laboratory lead to the purification and characterization of an anti-proliferative lectin (MLL) from the leaves of this plant. Further to that, here we have investigated the mechanism of cell death induction by MLL on human breast cancer (MCF-7) and colon cancer (HCT-15) cells. Cells were treated with GI(50) concentration (concentration of lectin required for 50% inhibition of cell growth) of MLL (8.5 μg/ml for MCF-7 and 16 μg/ml for HCT-15) for 24 h to induce cell death. The induction of apoptosis was studied by morphological analysis, DNA fragmentation, apoptotic cell staining and caspase 3 activity assay. Apoptotic cells in sub G0-G1 phase were monitored using flow cytometry. MLL induced significant morphological changes and DNA fragmentation associated with apoptosis in MCF-7 and HCT-15 cells. Positive annexin V and acridine orange/ethidium bromide stained cells indicated apoptosis induction by MLL. Up-regulation of caspase 3 activity was also found in cells treated with MLL. Flow cytometry analysis showed an increase in the percentage of cells in sub G0-G1 phase confirming the MLL induced apoptosis. In conclusion, MLL induced apoptosis in MCF-7 and HCT-15 cells in a caspase dependent manner.