The leaves of Mirabilis jalapa L contains protein fraction presumed ribosome-inactivating protein(RIP). RIP is a group of protein that has RNA N-glycosidase activity that is capable to inhibitprotein synthesis. Protein fraction of the plant was shown to be cytotoxic on HeLa cell-line,however, the mechanism by which the protein kill the cells is not identified yet, whether troughapoptosis, necrosis, or other mechanism. This research aim to study the mechanism of cell deathcaused by the protein fraction isolated from the leaves of this plant on HeLa and Raji cell-line, asrepresentative of different kind of cancer cells. Results showed that protein fraction isolated fromthe leaves of Mirabilis jalapa L was more cytotoxic to HeLa cell-line (LC50: 0.65 mg/ml) than toRaji cell-line (1.815 mg/ml) on 48 hours incubation time. Moreover, it was demonstrated that thedeath of HeLa cells caused by the protein fraction was due to induction of apoptosis, while onRaji cell-line was due to non-apoptosis way, presumably via necrosis.