Two novel rare earth tungstosilicic polyoxometalate containing 5-fluorouracil, K26(C4H4FN2O2)8Pr(SiW11O39)4·10H2O (FPSW) and K26(C4H4FN2O2)8Sm(SiW11O39)4·9H2O (FSSW), were synthesized and their structure were characterized by using elemental analysis, FTIR spectra, X-ray powder diffraction and TG. The antitumor activity tests of the compounds FPSW and FSSW were carried out by the methyl thiazolyl tetrazolium method in hepatocellular carcinoma cell HepG-2. The results showed that FPSW and FSSW could inhibit the HepG-2 cells in vitro significantly. The EC50 of FPSW and FSSW is 1.94×10-5 and 1.32×10-5 mol·L-1 respectively. The therapeutic index of FPSW and FSSW is 0.76 and 1.58 respectively.