Fucoidan induces apoptosis by activating caspase-8 in human MCF-7 breast cancer cells, but the detailed mechanism for this is not understood. We demonstrate here that fucoidan interacted with the cell surface, and silencing the β1-integrin gene expression inhibited fucoidan-induced apoptosis accompanied by caspase-8 activation. Fucoidan induced formation of the β1-integrin-caspase-8 complex. These data indicate that β1-integrin is an important factor for the cell-surface binding of fucoidan and plays an important role in fucoidan-induced apoptosis. Fucoidan also induced recruitment of caspase-8 to the β1-integrin intracellular domain, cleaved it into the activated protein by direct combination with β1-integrin, and induced apoptosis via the caspase cascade in MCF-7 cells.