Calcium sulfate hemihydrate (CSH) was introduced into the mineralized collagen (nHAC) to prepare an injectable and self-setting in situ bone graft substitute. The mechanical properties of materials, which are dependant on the L/S ratio, the content of nHAC and setting accelerator, were discussed based on the satisfying injectability and setting properties. It was found that the compressive strength and modulus of materials increased with the decrease of nHAC content and L/S ratio. CSD as setting accelerator hardly had an effect on the compressive properties of materials because it is not only the reactant of preparing CSH but also the final solidified product of CSH instead of a foreign body. Though the compressive properties of nHAC/CSD composites changed with the variety of nHAC content and L/S ratio, the compressive strength and modulus of the materials ranged from 2.0 to nearly 20.0 MPa and 100.0 to 800.0 MPa, respectively, which are similar to that of cancellous bone. In vitro cell behavior demonstrated that the composites could provide adequate environment for cell adhesion and proliferation. All these indicated that the nHAC/CSH composites were a potential scaffold for bone tissue engineering.