Aim: Portulaca oleracea and Portulaca quadrifida are found growing as weed in Asia, Africa, and parts of Mediterranean region. These plants belonging to the family Portulacaceae have been used in traditional systems of medicine in Asia and Africa for their pharmacological activities. This study was conducted to study the in-vitro cytotoxic activities of extracts of these plants on established cancer cell lines. Methods: Morphological observations, MTT assay and DNA fragmentation assay were employed to investigate their activity against HeLa and MCF-7 cancer cell lines. Result: All the extracts exhibited cytotoxicity at higher concentrations and the P. oleracea seed extract was found to be most active amongst the extracts studied. Cytotoxicity of P. quadrifida harvested from western India has not been reported in detail in literature and this study helps to compare the cytotoxicity of these closely related plant species. The phytochemicals previously identified from these extracts have been reported to possess cytotoxic activity which may help explain the observed cytotoxic activity against cancer cell lines. Conclusion: Although the crude extracts of the two plant species exhibit cytotoxicity to cancer cell lines in-vitro, further invitro and in-vivo studies using isolated phytochemicals from these extracts may provide a source of potential anti-cancer phytochemicals.