Fucoidan is an active component of seaweed, and could inhibit proliferation and induce apoptotic cell death in several tumor cells. However, the function of fucoidan in breast cancer is largely unknown. In the present study, we evaluated the anti-cancer potential of fucoidan in human breast cancer MCF-7 cells. Adult Sprague–Dawley rats were randomized to receive fucoidan (200 or 400 mg/kg·body weight per day) or normal saline via gastric gavage for 3 consecutive days. Serum samples were prepared from these rats, and used for subsequent experiments to examine the potential effects in MCF-7 cells. Cell viability was determined using a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Apoptosis was examined with Hoechst33258 staining and flow cytometry. Cell migration and invasion were measured by wound scratch assay and Transwell assay, respectively. Western blot and enzyme-linked immunosorbent assay (ELISA) were used to examine the expression of secretory E-cadherin and matrix metalloproteinase-9 (MMP-9). Conditioned serum from fucoidan-treated rats significantly suppressed cell proliferation and enhanced apoptosis. Cell migration and invasion were also significantly decreased. Observed effects of conditioned serum were associated with upregulation of E-cadherin and downregulation of MMP-9. Conditioned serum of rats treated with fucoidan could inhibit the proliferation and promote apoptosis of MCF-7 cells. Cell invasion and migration were inhibited, possibly via decreased epithelial–mesenchymal transition (EMT) process. Fucoidan may be a promising therapeutic agent for human breast cancers.