3-acetylcoumarin hydrazone scaffolds, synthesized from 3-acetylcoumarin and substituted benzoic acid hydrazides are reported with structural characterization using IR, HRMS, 1H and 13C-NMR. The In vitro anticancer activities against three human cancer cell lines viz. MCF-7 (human breast cancer cell line), HeLa (human cervical cancer cell line) and SCC-40 (human oral squamous cell carcinoma) are carried out while the tumour selectivity of compounds are tested on the normal human peripheral blood mononuclear cells (PBMCs). The compounds 3ACOH, 3ACDH and 3ACMH exhibited higher sensitivity towards HeLa with GI50 values between 20.4 - 44.1μg/ml and this range of GI50 concentration of hydrazones showed no remarkable toxicity against normal PBMCs. Molecular docking studies revealed commendable binding interactions with cyclooxygenase enzyme (PDB ID 6COX). ADMET analysis shows the hydrazones are showing drug-likeness properties. The reported observations of 3-acetylcoumarin hydrazones suggest their possible role as promising new anticancer drug candidates.