Two rare earth substituted Keggin-type phosphotungstates containing 5-fluorouracil, K 10 C 4 H 4 FN 2 O 2 Y(PW 11 O 39 ) 2 10H 2 O (FYPW) and K 9 (C 4 H 4 FN 2 O 2 ) 2 La(PW 11 O 39 ) 2 18H 2 O (FLaPW) were synthesized in aqueous solution, and the structures were characterized by Fourier transform infrared spectroscopy (FT-IR), element analysis, inductively coupled plasma spectrometry (ICP), X-ray powder diffraction (XRD) and 1 H nuclear magnetic resonance (NMR). Thermal analysis showed that the decomposition processes of the two compounds could be divided into three steps, the loss of crystal water, the decomposition of 5-fluorouracil unit and the decomposition of Keggin-type polyanions. The in vitro cytotoxicities against HEK 293, HeLa and HepG-2 cells were studied by methyl thiazolyl tetrazolium (MTT) assay. The results showed that FYPW and FLaPW had higher antitumor activities than 5-fluorouracil, C 4 H 4 FN 2 O 2 H 2 PW 12 O 40 8H 2 O and rare earth substituted polyoxometalates K 11 Ln(PW 11 O 39 ) 2 nH 2 O (Ln=Y, La). It was concluded that introducing 5-fluorouracil and rare earth (Y or La) into its structure was a considerable way to enhance antitumor activities of polyoxometalates.