SPG-56 is a newly isolated glycoprotein from sweet potatoes (Zhongshu NO. 1), but its value for suppressing breast cancer progression remains unknown. This study was designed to investigate the potential anti-cancer effects of SPG-56, which consists of 2.9% sugar and 97.1% protein. The effects of SPG-56 on the proliferation and apoptosis of breast cancer cells were determined using CCK-8 and Hoechst 33342 assays and flow cytometry, after staining with Annexin V and PI respectively. The activities of SPG-56 against breast cancer were examined using female BALB/c nude mice orthotopically implanted with human breast carcinoma cells of the types MCF-7 and 4T1-Luc. The cellular experiments showed that SPG-56 inhibited proliferation and promoted apoptosis of MCF-7 cells dose- and time-dependently. Oral administration of SPG-56 significantly suppressed the development of MCF-7 tumor cells (P?0.01) as compared with an untreated group. The serum tumor markers CEA, CA125 and CA153 in a 240?mg/kg/d SPG-56 decreased by 54.8%, 91.8%, and 90.3%, respectively. The experiments further demonstrated that SPG-56 inhibited the metastasis of breast cancer in MCF-7 and 4T1-bearing mice by altering the expression of MMP2, MMP9, VEGF, Occludin and Claudin. It is concluded that SPG-56 may have potential as a novel anti-tumor candidate for breast cancer.