To synthesize a series of 3-, 4-, and/or 11-trihydroxy modified bergenin derivatives and evaluated their cytotoxic activity in vitro. The phenolic hydroxyl groups of bergenin were protected by benzyl groups with benzyl bromide. Treatment of dibenzyl bergenin with the corresponding acid in the presence of EDC·HCl and DMAP in CH2Cl2, followed by hydrogenation over Pd/C catalysts, afforded derivatives of bergenin esters. All of the target compounds were identified by IR, MS, and 1H NMR. Twenty-six novel and three known derivatives of bergenin esters were synthesized. Their cytotoxicity values were evaluated by the MTT assay on the inhibition of DU-145 and BGC-823 cells in vitro. Several triply-substituted(3a, 4a, 5a, 6a, 7a) and doublysubstituted(8b, 9b) bergenin derivatives exhibited higher cytotoxic activity than bergenin. The result showed that the size of substituents and the lipophilicity of the bergenin esters displayed an important role on their cytotoxic activity. To synthesize a series of 3-, 4-, and / or 11-trihydroxy modified bergenin derivatives and evaluated their cytotoxic activity in vitro. The phenolic hydroxyl groups of bergenin were protected by benzyl groups with benzyl bromide. Treatment of dibenzyl bergenin with the corresponding acid in the presence of EDC · HCl and DMAP in CH2Cl2, followed by hydrogenation over Pd / C catalysts, afforded derivatives of bergenin esters. All of the target compounds were identified by IR, MS, and 1H NMR. Twenty-six novel and three known derivatives of bergenin esters were synthesized by the MTT assay on the inhibition of DU-145 and BGC-823 cells in vitro. Several triply-substituted (3a, 4a, 5a, 6a, 7a) and doublysubstituted 8b, 9b) bergenin derivatives Packaging said more cytotoxic activity than bergenin. The result showed that the size of substituents and the lipophilicity of the bergenin esters displayed an important role on their cytotoxic activity.