A new series of estrone base carbohydrazide has been designed and synthesized. Characterization and in vitro antimalarial evaluation of the newly synthesized compounds are discussed. Estrone and 4’-bromomethyl-2- cyanobiphenyl reacted in presence of potassium carbonate and potassium iodide in anhydrous acetone leads ether 4’-(3-yloxymethyl)-estrone-biphenyl-2-carbonitrile formation, which on sequential condensation with hydrazine hydrate and acid chloride give steroidal carbohydrazide in quantitative yield. Their structures were confirmed by Mass spectra, IR spectra and 1H, 13C NMR spectroscopy. The formation of carbohydrazide linkage with different acid chlorides had an excellent effect on the activity of the compounds. The newly synthesized steroidal carbohydrazide are screened for antimalarial activity against the P. Falciparum.