A series of 2-(2,3,4-trimethoxyphenyl)-1-(substituted-phenyl)acrylonitrile (2-9) were designed and synthesized to develop new cancer drugs. The structures of synthesized compounds 2-9 were described by using melting point, mass (MALDI-TOF-MS), FT-IR, elemental analysis, H-1, C-13, C-13-APT and 2D NMR spectroscopy. The in vitro anticancer activities of 2-9 against human breast cancer (MCF-7), human prostate cancer (PC-3) and human ovarian cancer cells (A2780) were investigated by [3-(4,5-dimethylthiazol)-2-yl]-2,5-diphenyl-2H-tetrazolium bromide] (MTT) assay method. Additionally, the LogIC(50) values of these compounds on A2780, MCF-7 and PC-3 cell lines were calculated by using inhibition % values by the GraphPad Prism 6 program on a computer. The results indicated that these compounds have high anticancer activity against MCF-7, PC-3 and A2780 cell lines (especially A2780 cell lines, p < 0.05).