Indanones are very useful molecules as starting building blocks for the synthesis of biologically active compounds. A series of novel curcumin-related compounds containing indan-2-one were synthesized and screened for anticancer activities. The structures were confirmed by spectral data (IR, NMR, and Mass). Inhibitory effects of these compounds on the growth of prostate cancer PC-3 cells, pancreatic cancer BxPC-3 cells, colon cancer HT-29 cells, lung cancer H1299 cells and non-tumorigenic human prostate epithelial RWPE-1 cells were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The IC50 for compound IND-4 was lower than 1 µM in the four cancer cell lines. The present study indicates that IND-4 may have useful effects on human cancer cells.