A series of difluorinated propanediones were synthesized and evaluated for in vitro cytotoxic activity by Sulforhodamine B (SRB) assay against a panel of four human cancer cell lines. Though the compounds showed varying degrees of cytotoxicity in the tested cell lines, most marked effect was observed in breast cancer cell line (MCF7), wherein nine of the ten synthesized chalcones showed good antiproliferative activity.