In the metamorphosis of silkworms, 20-hydroxyecdysone(20E) facilitates apoptosis and autophagy, thereby promoting the degeneration and remodeling of larval organs.This process represents a promising target for the development of environmentally friendly insect control methods. However, the primary impediment to realizing this goal is the incomplete understanding of the mechanisms underlying 20E action. Our previous research has identified Bmp53 as a crucial gene in promoting the development of B. mori during the pupal stage by inducing apoptosis, and has predicted the potential apoptotic regulatory network of Bmp53,including the Mdm2-like ubiquitination structural protein. Present research findings indicate that the Mdm2-like functions as a ubiquitination regulatory protein, modulating its apoptosis-inducing capability through interaction with Bmp53. Furthermore, the co-expression of Mdm2-like and Bmp53 has been shown to indirectly influence the gene expression within the 20E-mediated apoptosis pathway. Subsequent research revealed that Mdm2-like could attenuate the apoptosisinducing effect of 20E by downregulating Bmp53 expression. This study has confirmed that the ubiquitination apoptosis regulation pathway involving in Mdm2-like/Bmp53 constitutes a novel mechanism for apoptosis regulation in silkworms and potentially other lepidopteran insects.Additionally, it has been determined that 20E plays a significant role in this pathway. The findings of this research contribute to a deeper understanding of the genetic underpinnings of tissue degradation during the metamorphic stage of the lepidopteran model insect, the silkworm.Furthermore, these insights provide a theoretical foundation for the development of environmentally friendly hormone-based control strategies aimed at disrupting protein modification as a means of lepidopteran pest management.