Hepatocellular carcinoma (HCC) is the most common liver cancer, accounting for approximately 90%, and it has a five-year survival rate around only 30–40%. Similar to other kinds of cancers, tumor metastasis remains the primary cause of mortality of HCC patients. It is well known that metastasis is a multistage process that requires cancer cell detachment from the primary tumor, survival in the circulation, settlement at distant sites and growth. During this process, metastatic cells go through detachment, migration, invasion and adhesion, and inhibition of any one of these steps has the potential to block the entire metastatic process. However, there is very little advancement in the area of blocking tumor metastasis, therefore, new effective agents possessing anti-metastasis activities are urgently needed for better prevention and treatment of HCC and other cancers. Our previous results suggested that EPS11, a novel marine bacterial polysaccharide, might be a potential drug candidate for human non-small cell lung carcinoma treatment. In this study, we further investigate the anticancer mechanisms against liver cancer and the anti-metastatic effects of EPS11.