Tissue engineering (TE) is an emerging and promising strategy to heal tissue failure by integrating science and technology of materials, cells and growth factors. With the increasing of aging population, restoring musculoskeletal tissue has become the focus of TE. Among various materials tested in TE, silk fibroin (SF) is increasingly being recognized as a promising material. SF, a natural protein polymer with excellent physiochemical characteristics, has established a good reputation in terms of musculoskeletal tissue engineering (MTE). The present article provides an overview of SF and introduces various approaches of fabricating SF-based biomaterial followed by their applications in MTE.