Four matrine derivatives were synthesized by Claisen-Schimidt condensation in which matrine reacted with anisaldehyde or veratrum aldehyde or 3,4,5-trimethoxy-benzaldehyd or 2,3,4-trimethoxy-benzaldehyd in sodium hydride solution. The most suitable condition for the synthesis was decided by the orthogonal experiment. Inhibitory effects of these compounds were determined by the MTT assay on the growth of HT-29 cells and PANC-1 cells. These compounds exhibited better inhibitory effects than matrine . Four matrine derivatives being synthesized have better anticancer activity than matrine.