In this research, the preparation and evaluation of poly (lactic-co-glycolic acid)/nano biphasic calcium phosphate (PLGA/nano-BCP) for bone tissue engineering has been investigated. First, the preparation and properties of nano-composite scaffolds for bone tissue engineering were briefly reviewed. Then, the BCP fabrication process was carried out by burning and heat treatment of cortical and cancellous bovine bones. After that, the bioactivity in SBF solution, and cytotoxicity of the resultant nano-BCP powders, by MTT assay of G-292 osteoblast cells, were evaluated. The results showed that after immersing the bones in di-ammonium hydrogen phosphate ((NH 4 ) 2 HPO 4 ) solution and subsequent heat treating at the temperature range of 700 to 1300 ?C, the calcined hydroxyapatite transformed to HA/?-TCP biphasic structure. By increasing the heat treatment temperature, the amount of ?-TCP phase in the samples increased in such a way that cancellous bone samples were entirely converted into ?-TCP at 1300 ?C. SEM images, EDS and XRD analysis of immersed samples in SBF solution showed that a uniform layer formed on the surface after 28 days with the chemical composition of hydroxyapatite. Cytotoxicity assay of the nano-BCP (nBCP) powders extract, with the chemical composition of HA/?-TCP: 60/40, in contact with osteoblast G-292 cells revealed that the nBCP compounds do not show cytotoxicity. Moreover, the rate of cell proliferation for nBCP is greater than nHA. In the rest of this study, PLGA, PLGA/nBCP and PLGA/nHA scaffolds were fabricated, by thermal induce phase separation (TIPS), and their properties were compared for use in bone tissue engineering . The freeze dryer was applied to fabricate scaffolds at a temperature of -60 ?C and pressure of 0.04 mbar. The scaffolds had more than 89% porosity with an average pore size of 60 to 150 µm. TIPS process is one of the most common and inexpensive methods for fabrication of polymer matrix nano-composite scaffolds with very high amount of porosity. The mechanical and in vitro degradation properties of PLGA and PLGA/nBCP scaffolds were evaluated and their cell behavior was investigated under cell culture tests. The results of tensile tests showed that the yield strength of the PLGA/nBCP composite scaffold with 30 wt% nBCP particles was about 0.54 MPa which was higher than other samples. By addition of 30 wt% nBCP to PLGA matrix, a more uniform distribution of particles and less agglomeration was observed in comparison to composite scaffolds containing 40 and 50 wt% particles. With increasing the amount of particles in the scaffold, the elastic modulus of scaffolds were increased so that the elastic modulus of PLGA/50 wt% nBCP (14.83 ± 0.83 MPa) was about 8.7 times higher than the base PLGA scaffold. The nBCP reinforcement particles in the composite scaffolds, due to their high surface energy and strong bonds with the polymer matrix, can increase the modulus of elasticity and yield strength of the resultant composite. Degradation tests showed that the weight loss of the PLGA/nBCP composite scaffolds were more than that of PLGA scaffolds and by increasing the amount of nBCP particles in the composite scaffolds, the rate of weight loss increased. The weight loss affected the mechanical properties of scaffolds, significantly in such a way that after immersion in solution for 8 weeks, the yield strength and elastic modulus dropped to negligible values and the scaffolds were ruptured easily. Also, MTS assay for L-929 fibroblast cells and MG-63 osteoblast cells in contact with PLGA and PLGA/nBCP composite scaffolds (with 30, 40 and 50 wt% nBCP particles), showed that cell viability and proliferation for composite scaffolds were more than pure polymer scaffolds. Addition of nBCP reinforcement particles in the range of 30 to 50 wt% significantly enhanced the cell behavior of composite scaffolds and can provide a suitable condition for the repair of injured bone tissue. In conclusion, it can be stated that the PLGA/nBCP scaffolds with 30 wt% nBCP have better mechanical and degradation properties and cell behavior than other scaffolds. Key words: Biphasic calcium phosphate, Poly (lactic-co-glycolic acid), Nano-composite(s), Scaffold(s), Hydroxyapatite, Bioactivity, Degradation, Bone tissue engineering