Abstract: The ideal artificial bone repair materials should possess good in vitro biocompatibility and in vivo osteogenesis. In this study, Poly (amino acid)/Selenium doped Hydroxyapatite (PAA/Se-HA) composite was prepared, followed by coating of Se-HA via Polydopamine (PDA) bridge for constructing Se-HA@PDA@PAA/Se-HA composite. The physical and chemical properties were evaluated by X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FT-IR), Thermogravimetric Analysis-Differential Scanning Calorimetry (TG-DSC), Scanning Electron Microscopy (SEM) and mechanical properties. The protein adsorption experiment was evaluated for assessing whether the surface of composite was beneficial for cell adhesion. The concentration of selenium released from composites was detected by inductively coupled plasma mass spectrometry (ICP-MS). The extract of PAA, PAA/Se-HA and Se-HA@PDA@PAA/Se-HA was prepared, and the extract prepared above was used for culturing bone marrow mesenchymal stem cells (BMSCs) so as to evaluate the in vitro biocompatibility of the composite through cell proliferation experiments and cell morphology observation. The property of osteogenic differentiation of BMSCs induced by samples was assessed by alkaline phosphatase activity (ALP) assay. The in vivo osteogenic properties of PAA, PAA/Se-HA and Se-HA@PDA@PAA/Se-HA composite were evaluated by implantation of samples into the femoral condyle defect of New Zealand white rabbits. The result shows that the Se-HA@PDA@PAA/Se-HA composite exhibits both the chemical characterization of PAA and Se-HA, and the Se-HA particles can be uniformly dispersed in the matrix and the surface of PAA/Se-HA composite. The melting temperature and the maximum weight loss temperature of PAA/Se-HA30 composites were about 210 ℃ and 461 ℃, respectively. The compressive strength, bending strength and yield strength of this composite were about 104MPa, 80 MPa and 96 MPa, respectively. In comparison with PAA and PAA/Se-HA composite, Se-HA@PDA@PAA/Se-HA composite possesses high protein adsorption value, indicating conducive of cell adhesion. After 3 days culture of BMSCs with extract of composite, the cells show obvious proliferation, indicating good cell compatibility of composite. After 7 days culture of BMSCs with extract of composite, the Se-HA@PDA@PAA/Se-HA composite display great property of inducing osteogenic differentiation of BMSCs in comparison with PAA/Se-HA composite. The in vivo result possesses that the composite could guide new bone formation and formed strong bond with new bone tissue after 6 weeks implantation. In summary, Se-HA@PDA@PAA/Se-HA composite has good mechanical properties and thermal stability. And it could promote the proliferation and osteogenic differentiation of BMSCs in vitro, and osteogenesis in vivo, which might be a promising biomaterial in the field of bone tissue engineering.