Abstract: A new salt leaching method was developed to make 3D porous silk fibroin scaffolds. The human osteosarcoma cells(MG-63), fibroblasts(NIH-3T3) and liver cells (HepG2) were cultured on the porous silk fibroin scaffolds and the cells compatibility on the scaffold was investigated. It is found that the cell compatibility is good and the structure and property of 3D scaffold could be controlled by adjusting the concentration of silk fibroin aqueous solution, dissolved fibroin solvent system, the amount of salt added and the NaCl particle size. Compared with traditional silk fibroin-based materials, this research offers an entirely new window to prepare the materials of porous silk fibroin scaffolds.