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With the advent of the internet of things and artificial intelligence, flexible and portable pressure sensors have shown great application potential in human-computer interaction, personalized medicine and other fields. By comparison with traditional inorganic materials, flexible polymeric materials conformable to the human body are more suitable for the fabrication of wearable pressure sensors. Given the consumption of a huge amount of flexible wearable electronics in near future, it is necessary to turn their attention to biodegradable polymers for the fabrication of flexible pressure sensors toward the development requirement of green and sustainable electronics. In this paper, the structure and properties of silk fibroin (SF) are introduced, and the source and research progress of the piezoelectric properties of SF are systematically discussed. In addition, this paper summarizes the advance in the studies on SF-based capacitive, resistive, triboelectric, and piezoelectric sensors reported in recent years, and focuses on their fabrication methods and applications. Finally, this paper also puts forward the future development trend of high-efficiency fabrication and corresponding application of SF-based piezoelectric sensors. It offers new insights into the design and fabrication of green and biodegradable bioelectronics for in vitro and in vivo sensing applications.