Under solvent free conditions and in presence of a base 3-(2-(subsituted-(trifluoromethyl)phenylamino)acetyl)-2H-chromen-2-one derivatives were synthesized by grinding technique. Structural investigations were carried out with IR studies, HRMS, 1HNMR and 13CNMR. The compounds were checked for their in vitro anticancer activities against three different human cancer cell lines viz human breast cancer cell line (MCF-7), human cervical cancer cell line (HeLa) and human oral squamous cell carcinoma (SCC-40) using SRB method. All the title compounds showed low toxicity towards non-malignant PBMC cells indicating their tumour selectivity. The compounds exhibited good in vitro anti-proliferative potency at lower concentrations against HeLa and MCF-7 cell lines and remain moderately active against SCC-40.