The universal incidence and tremendous mortality ratio of cancer makes it a serious health affair especially in cancers progressive with inflammation. In view of this menace, consequential efforts are continuing to characterize new drugs or agents for therapeutic intervention against cancer. As a follow through, herein our study a series of 9-Anthracenyl chalcone derivatives (A1–A16) were designed, synthesized, characterized and evaluated for their anti-cancer activity against four human cancer cell lines HeLa, MIAPACA, U-87 and SIHA using an SRB assay. Among them we found that four of the compounds A7, A8, A10 and A11 have shown marked anti-cancer activity against HeLa, U-87, MIAPACA and SIHA with GI50 values of 5.18 μM, 4.04 μM, 5.31 μM and 4.02 μM respectively.