In this study, a novel Sr-based bulk metallic glass (BMG) with nominal composition of Sr40Mg20Zn15Yb20Cu5 (at.%) was fabricated with high-purity raw materials by induction-melting method. Its mechanical properties, corrosion behavior, and cellular compatibility were studied in vitro as a feasibility evaluation of potential biodegradable metal. The compression strength of Sr40Mg20Zn15Yb20Cu5 alloy was (408.2 ± 20.0) MPa, which was much higher than human bone (164–240 MPa). Its Young's modulus (20.6 ± 0.2) GPa was quite close to human bone (5–23 GPa). MTT assay and PNPP method were employed to measure the proliferation ability and ALP activity of the experimental Sr-based BMG. The results 0–1 grade cytotoxicity and high ALP activity revealed that it was harmless to osteoblast-like MG63 cells. Additionally, the cells cultured on the surface of Sr40Mg20Zn15Yb20Cu5 alloy plate exhibited polygonal and dorsal ruffle configuration, and were well attached to the substrate by cellular extension, indicating their healthy status. The combination of increased mechanical strength, greater corrosion resistance, and excellent biocompatibility makes the Sr40Mg20Zn15Yb20Cu5 BMG very attractive material for biodegradable orthopedic implant applications. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 100B: 368–377, 2012.