Here, we present a new process for the preparation of cellulose-silk fibroin hydrogels using a concentrated lithium bromide (LiBr) aqueous solution. After mixing, the solutions of cellulose and silk fibroin that had each been dissolved separately in aqueous LiBr, the cellulose forms a gel as the solution cools to approximately 70 degrees C, and silk fibroin is regenerated via treatment in methanol. Three grades of cellulose-silk fibroin hydrogels are prepared by controlling the amounts of cellulose and silk fibroin. The gels have highly porous, three-dimensional networks composed of long, interconnected fibrils. Through X-ray diffraction and ATR-FTIR analysis we show that the dissolution-regeneration of cellulose and silk fibroin induces a structural change in the crystal structure of cellulose II and silk II. While the porosity and swelling ratio of cellulose-silk fibroin gels is significantly reduced with the increased silk fibroin content, all the gels show high water uptake. The enzymatic degradation rates of cellulose-silk fibroin gels obviously reflect differences in the silk fibroin content, and cell adhesion and growth on cellulose-silk fibroin gels is enhanced with increased silk fibroin content. These cellulose-silk fibroin gels could provide novel properties that would be useful for biomaterial matrix applications.