Abstract: A series of andrographolide derivatives with the structure of 12-N-substituted-14-deoxyandrographolide were synthesized from the parent compound andrographolide.Their antitumor activities were preliminarily evaluated on various cancer cell lines and compound 4d stood out due to its potent growth inhibitory effect in comparison with andrographolide.Compound 4d also demonstrated significant antitumor effect on human hepatoma HepG2 cells in vitro and on sarcoma 180 (S180) and hepatoma 22 (H22)-bearing mice in vivo.Then，the apoptosis induced by compound 4d in HepG2 cells was detected by Annexin V/PI double staining assay.Further mechanic study showed that the expression of p53 and Bax was significantly elevated and that of Bcl-2 was down-regulated in 4d -treated HepG2 cells.Collectively，these data suggested that compound 4d had remarkable antitumor effect both in vitro and in vivo and could effectively induce apoptosis via a p53-dependent pathway in HepG2 cells，thus deserving further investigation.