This work focuses the light on some remarkable achievements in clean and efficient green experimental synthesis, characterization and evaluation of the pharmaceutical and biochemical importance of new series of pyrazolo[1,2-b]phthalazinediones which synthesized through one-pot three-component condensation reaction of the appropriate of 1,2,3-triazolyl-pyrazole-carbaldehydes with active methylene compounds (as malononitriles or ethyl cyanoacetate) and 6-nitrophthalhydrazide using the grinding method in the presence of sodium hydroxide under solvent-free condition at room temperature, in very excellent yields. All the newly synthesized compounds were characterized by physical and chemical tools (FT-IR, 1H NMR and mass spectrometry). In addition, all the new synthesized derivatives were screened for their anticancer activity against hepatic cancer cell lines to evaluate their pharmaceutical importance.