Abstract: Objective To prepare a novel strontium-containing calcium sulfate and assess its and biocompatibility. Methods A novel strontium-containing α-calcium sulfate hemihydrate (Sr-caS) bone substitute as prepared with hydrothermal reaction and examined for X-ray diffraction (XRD), Fourier transform infrared (FTIR) and thermogravimetric differential scanning calorimetric (TG-DSC) patterns. The biocompatibility of the material was evaluated by in vitro cytotoxicity test in L-929 cells, hemolysis test of blood, and in vivo implantation test in SD rats. Results The XRD spectra of the prepared Sr-CaS powder highlighted 3 strong characteristic peaks of α-CaSO4 at 14.63°, 25.72° and 29.80° with a strontium-specific peak at 24.78°. The FTIR patterns of Sr-CaS resembled those of CaS. TG-DSC results showed that the material contained a non-evaporable water content of 6.03%. In vitro cytotoxicity test in L-929 cells suggested that the material had a class 1 cytotoxicity, and the hemolysis rate of its aqueous extract was 4.3%. The material implanted in the muscular tissues of SD rats maintained a steady state in the surrounding tissues. Conclusion This strontium-containing calcium sulfate material we prepared shows an excellent biocompatibility for potential use as a novel artificial bone material.