Bone grafts have been used to fill bone defects caused by disease or trauma. The amount of autografts is limited and allogenic bone grafts may transmit diseases and cause immune responses. Numerous materials have been proposed and used as scaffolds for bone tissue reconstruction. In this study, we tested nanophase PLGA/HA composite with mesenchymal stem cells in vitro to examine its biological response and cellular activity. The nanophase composite was compared to conventional polystyrene on cytocompatibility by cell attachment, proliferation, alkaline phosphotase activity test and scanning electron microscopy (SEM) analysis. The results demonstrated that human mesenchymal cells showed more cell attachment and higher cell proliferation rate when growing on nanophase PLGA/HA composite than those growing on polystyrene alone. And the composite also promoted MSC cells differentiate to osteoblast cells as compared with control. It was suggested that the combination of bone marrow mesenchymal cells with artificial materials or differentiation factors may enhance bone formation and regeneration, nanophase PLGA/HA composite might therefore be a promising scaffold material for bone tissue substitute in clinical application.