Background: cancer is basically a disease of uncontrolled cell division. Its development and progression are usually linked to a series of changes in the activity of cell cycle regulators. Objective: the present study aimed to investigate the anticancer potential of Echispyramidum venom against HepG2 and HCT 116 cancer cell lines in comparison with the Cisplatin as positive control. Patients and Methods: cell viability performed using MTT assay was cell type and concentration dependent was inversely proportional with the tow substances (Echispyramidum) venom as well as Cisplatin had IC50 of 11.8 and 112.7 µg/mL and 13.4 and 71.2 µg/mL developed in HCT116 and HepG2 cell lines respectively. Results: both of Echispyramidum venom and Cisplatin showed DNA accumulation at the Pre-G1 and G2/ M Phases of cell cycle. Apoptotic profile of treated cells showed up regulation of apoptotic genes (P53, Bax and Casp-3) and down regulation of anti-apoptotic gene (Bcl-2) in a significant way compared with untreated cell control. Also, apoptotic profile was assured via cellular changes detected microscopically in H&E stained cells. Microscopic examination showed apoptotic and slightly necrotic features in case of venoms while Cisplatin induced a number of apoptotic bodies and necrotic cell colonies. Conclusion: it can be concluded that Echispyramidum venom has a clear anticancer potential to human liver and colorectal cancer cells that was proven through the cell cycle arrest profile, induced apoptosis detected via detection of the levels of expression of pro and anti-apoptotic genes, as well as histological alteration detected.