Parthenium hysterophorus Linn (Compositae) is an obnoxious weed, native to America but has spread in many countries. We are reporting first time the comparative analysis of its different extracts (Methanol, Ethanol, Chloroform & Aqueous) for their anticancerous activity. It was found that all extracts were cytotoxic to the investigated human cancerous cell lines Ovary (IGROV- I), lung (A-549), prostate (PC-3), breast (MCF-7) & CNS (SF-295) except Lung cancerous cell line (HOP-62), determined by sulphorhodamine B (SRB) assay. These extracts were found to show significant activity which were measured in IC50 values. Flow cytometry confirmed that these extracts were found responsible for apoptosis when HL-60 cell line was incubated with Methanolic extract (found to be more active). Methanol extract was found to show highest cytotoxicity with IC50 of 0.11μM (PC-3). Although other three extracts showed significant cytotoxicity but did not follow a regular pattern. Overall, it was concluded that there is a bright hope to advance this lead into a capable anticancer therapeutics, however, to choose a better extract is a matter of screening, as different cells follow different molecular and signal cascade mechanisms.