In this study, the steroidal alkaloid veratramine, which is rich in Veratrum plants, was taken as the starting material for structure modification. Five veratramine analogs 2~6 were obtained. Their structures were determined by means of MS and NMR. Cyclopamine, the first inhibitor of Hedgehog signaling pathway, was used as the positive control, and the antiproliferative activities of yielded compounds on human grastric cancer cell SGC-7901 and human pancreatic cancer cell Aspc-1 in vitro were carried out. The results showed that the antiproliferative activities of compounds 4, 5 and 6 were much more potent than that of cyclopamine. Preliminary study of the structure-activity relationship suggested that antiproliferative activities of veratramine analogs could be increased by introducing appropriate hindering groups at piperidine ring of veratramine.