Objective: To explore the effect and the related mechanisms of fucoidan on hepatoma cell proliferation. Methods: Proliferation inhibition rate of hepatoma HepG2 cells was measured by MTT. A variety of dosage of fucoidan (0 μg/ml,10 μg/ml,100 μg/ml and 500 μg/ml) was treated to HepG2 cells. The morphology changes of the cells were observed under microscopy. Apoptosis was detected by Hoechst 33258 staining and DNA Ladder analysis. CyclinD1 and topoisomerase IIα(TopoIIα) were as the proliferation biomarker. Their protein expression levels were examined by Western blot. Results: Fucoidan inhibited HepG2 cells proliferation in a dose-dependent manner. There was a remarkable morphological change when cells were treated with 500 μg/ml of fucoidan. Apoptosis was occurred when the cells were incubated with 100 μg/ml and 500 μg/ml of fucoidan. In addition,fucoidan also suppressed the expression of cyclinD1 and TopoIIα in HepG2 cells. Conclusion: Fucoidan can inhibit the proliferation of HepG2 cells and induce apoptosis. Meanwhile,fucoidan also has the ability to suppress the protein expression of cyclinD1 and topoIIα,which may be involved in the mechanisms of inhibiting hepatoma cells proliferation.