Calcium sulfate (CS) bone cements have been used as bone substitutes for a long history, but it is limited to apply in clinical trials due to its rapid degradation rate and brittleness. This work aims to study the effect of α-tricalcium phosphate (α-TCP) and silk fibroin nanofibers (SFF) on the CS bone cements. The bone cements are prepared by α-calcium sulfate hemihydrate (α-CSH), calcium sulfate dihydrate (CSD) as setting accelerator, and varying α-TCP contents (0%, 5%, 10%, 15%, 20% and 25%), in which SFF or deionized water is the solidification solution at the same liquid/ solid (L/S) ratio. Scanning electron microscopy (SEM), particle size distribution, X-ray diffraction (XRD) and Fourier transform infrared (FTIR) are used to measure the composition and characterize the properties of the materials. Compressive strength, setting time and weight loss rate of samples are also tested. Furthermore, the cytotoxic is evaluated by Cell Counting Kit-8 (CCK-8) assay. The results suggest that the tuning of α-TCP and SFF play important roles in the compressive strength and degradation rate of CS bone cements, and the properties could be changed by varying the content of α-TCP. Moreover, cell experiment shows there exist had no toxic of MC3T3 cells on the samples. Thus, materials prepared by α-CSH, CSD, α-TCP and SFF in this work would provide the basis for the research of CS-based bone repair materials.© 2020 IOP Publishing Ltd.