Benzofuran derivatives are of great interest in medicinal chemistry and have drawn considerable attention due to their diverse pharmacological profiles including anticancer activity. Similarly, chalcones, which are common substructures of numerous natural products belonging to the flavonoid class, feature strong anticancer properties. A novel series of chalcones, 3-aryl-1-(5-bromo-1-benzofuran-2-yl)-2-propanones propenones (3a-f), were designed, synthesized, and characterized. In vitro antitumor activities of the newly synthesized (3a-f) and previously synthesized (3g-j) chalcone compounds were determined by using human breast (MCF-7) and prostate (PC-3) cancer cell lines. Antitumor properties of all compounds were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell viability assay for the tested chalcone compounds was performed and the log IC50 values of the compounds were calculated after 24-hour treatment. Our results indicate that the tested chalcone compounds show antitumor activity against MCF-7 and PC-3 cell lines (p < 0.05).