In tissue regenerative medicine, developing tunable degradation rate of biomaterials for predictive functional outcomes remains critical. The implanted scaffolds should degrade gradually along with the tissue regeneration, and the optimal degradation rate of scaffold depends on the tissue type to be regenerated. Herein, the tunable degradation rates of silk fibroin (SF) scaffolds were fabricated through controlling dissolution, hydrolyzing conditions, and freeze-drying. The pore size, water adsorption capacity, and mechanical properties of scaffolds were associated with their average molecular weights. Moreover, in vitro cytotoxicity tests demonstrated that rapid degradation of SF scaffolds would facilitate the Schwann cells proliferation. Furthermore, in vitro enzymatic degradation and in vivo subcutaneous implantation experiments illustrated that SF scaffolds degradation behaviors could be well regulated. Immunohistochemistry staining experiments suggested that SF scaffold-degradation products could promote the endothelial cells proliferation. These results indicate that SF tunable degradation rates are promising candidates in regenerative medicine.