In the present study, we investigated the effects of starfish (Asterina pectinifera) polysaccharides on cancer proliferation and metastasis in HT-29 human colorectal adenocarcinoma. Cytokine-stimulated expression of inducible nitric oxide synthase (iNOS), which is closely associated with cancer proliferation, invasion and metastasis, was dose-dependently diminished by treatment with the starfish polysaccharides. 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced activity and expression of matrix metalloproteinase (MMP)-2, a major inducer of metastasis in colorectal cancer, were also down-regulated in a dose-dependent manner. In contrast, tissue inhibitor of matrix metalloproteinase (TIMP)-1 and -2 mRNA, which play critical roles in preventing metastasis, increased over the polysaccharides concentration range $10{sim}120{mu}g/mL$. In the wound healing assay, HT-29 human colorectal adenocarcinoma migration activated by TPA was decreased by treatment with the starfish polysaccharides. These results indicate that the starfish polysaccharides inhibited human colorectal cancer proliferation and metastasis by preventing nitrogen oxide synthesis, which occurred via inhibition of iNOS and MMP-2 activity and expression and induction of TIMP-1 and -2 expressions. This report demonstrates that starfish polysaccharides may be used as an anti-proliferation and -metastatic material for the treatment of human colorectal cancer.