A series of novel glyco-gambogic acid (GA) compounds were synthesized and evaluated for their in vitro anti-proliferative activity against human hepatocellular carcinoma (HCC) cells.All compounds showed much better aqueous solubility (0.92-1.89 mg/mL) than GA (0.013 mg/mL),and displayed potent inhibition on HCC cells (IC50:0.21-12.23 μmol/L) and little affects on non-tumor liver cells (IC50:42.56-86.43 μmol/L),suggesting that glyco-GA compounds selectively inhibit HCC proliferation,and may be promising candidates for further intensive study.