The development of a portable, controllable, and environmentally friendly electronic skin (e-skin) is highly desirable; however, it presents a major challenge. Herein, a biocompatible, biodegradable, and easily usable hydrogel was designed and fabricated as e-skin to enable the transmission of information regarding the spatial pressure distribution. Silk fibroin (SF) was used as the hydrogel skeleton, which endowed the hydrogel with intelligent mechanical sensitivity. During its conditioning in weakly acidic media, the density of the enzymatic crosslink increased and a dense network was formed due to the formation of covalent/hydrogen bonds. Additionally, a conductive SF/polyvinyl alcohol (PVA) hybrid film was molded as a flexible electrode after graphite deposition. The above SF sensing unit based on SF hydrogels and SF/PVA hybrid films showed high strain sensitivity (4.78), fast responsiveness (<0.1 s), good cycling stability (≥10,000), excellent biocompatibility, and biodegradability. Importantly, a coplanar 8 × 8 pixel SF-based e-skin array was successfully fabricated and applied for 3D signal transmission of the object. The SF-based e-skin was capable of precisely tracking the changes in the pulse pressure, the movement of the finger joint, and the vibrations of the vocal cord. Therefore, the current findings provide a solid foundation for future studies exploring the next generation of electronic devices.