Silk fibroin (SF) hydrogels are explored for diverse applications, ranging from cosmetic thickeners to support matrices for drug delivery and regenerative medicine. However, their utilities remain inherent challenges in inadequate mechanical properties and sophisticated process. Hyaluronic acid (HA) is a natural polysaccharide with outstanding physiological activities and superior water retaining capacity. In this study, HA was used as a skeleton of interpenetrating network to fabricate SF/HA hydrogel with high-flexibility and micro or nanofibers networks. The flexibility and water-absorbing quality of SF/HA hydrogels are improved dramatically due to super hydrophilicity of HA addition. By the synergistic effect of HA and solvent exchange, SF molecular conformation is induced efficiently to form β-sheet structures and assembling directly by physical crosslinking, which are determined by structure analysis. Moreover, the condense structure of the SF/HA hydrogel is mainly silk II, which contributes to their high thermal stability. The HA also plays a dominating role in formation of the micro or nanofibers networks on the wall of the SF/HA hydrogels, confirming by elements analysis. Investigation on fibroblast vitality and morphology showed that these SF/HA hydrogels can support cell adhesion, differentiation, and proliferation in vitro and present a better biocompatibility in comparison to pure SF hydrogel. Thus, it is believed that this work provides a facile way to fabricate protein-polysaccharide biomaterials and tissue engineering scaffolds.