Cells are exposed to mechanical stress, such as fluid shear stress (FSS), mechanical strain, hydrostatic pressure in vivo. FSS is considered to be the most important stress during bone homeostasis and remodeling. At present, most studies are mainly about the FSS effect on osteocytes and osteoblasts. However, the effects of FSS on bone mesenchymal stem cell (BMSCs) are not fully understood. BMSCs are of great significance in bone reconstruction and clinical treatment, so researchers increasingly focus on the response of BMSCs to FSS. The response of BMSCs to FSS depends on the alteration of cytoskeleton, matrix stiffness and elasticity, osteogenic signaling pathways and so on. In this review paper, the recent researches about the mechanotransduction mechanism of FSS, and its effect on differentiation and function of BMSCs are summarized, so as to provide new insights for studying construction of tissue engineered bone and treatment of bone diseases.