Abstract: The small ubiquitin-like modifications regulated by small-like modifier specific protease (SENPs) plays an important role in the regulation of radiosensitivity, and inhibition of SENPs will increase the radiosensitivity of tumor cells. According to reports, SENPs regulates the radiosensitivity of tumor cells by participating in DNA damage repair, altering cell cycle distribution and regulating signal pathways. At present, SENP1-based SENPs inhibitors are mainly divided into several types including small hairpin RNA, peptides and peptidomimetics, synthetic small molecules, compounds derived from virtual screening and natural products. SENPs inhibitors can be used as new types of radiosensitizers, which need to be further optimized and developed. In this review, we discuss the potential mechanisms of SENPs regulating radiosensitivity and the research progress of its inhibitors to lay a theoretical foundation for the subsequent development of SENPs inhibitors as radiosensitizers.