One pot four component, environmentally benign synthesis of 1H-indol-2-yl-5,10-dioxo-5,10-dihydro-1H-pyrazolo[1,2-b]phthalazine-2-carbonitrile derivatives was achieved in the presence of ionic liquid [bmim][OH]. The multi component reaction occurs with an initial formation of pthalazine followed by its reaction with the Knoevenagel cyclocondensation product of indole aldehyde and malononitrile/ethyl cyanoacetate in the presence of [bmim][OH] as ionic liquid at 70-75 oC for 30-45 min. All the synthesized pthalazine indolyl analogues have been tested for their anti-cancer activity on breast and lung carcinoma cell lines. Among the tested derivatives, 5b, 5c, 5e, and 5f found to be active against the cancer cell lines. Further, molecular modeling studies were performed to understand binding pattern of the top active molecules with the target protein.