We previously carried out a genome-wide transgenic RNAi screen in adult Drosophila intestines and identified soluble N-ethylmaleimide-sensitive factor-attachment protein alpha (αSnap), which regulates the survival of intestinal stem cells (ISCs). To further elucidate the function of αSnap in ISC survival, we performed a series of immunofluorescence staining experiments. Our results revealed that the ablation of αSnap in ISCs results in cell death through necrosis rather than apoptosis. The absence of αSnap triggers a series of cellular senescence cascades in the Drosophila gut and brain, including lipid droplet (LD) accumulation, the formation of protein aggregates, mitophagy activation, and elevated reactive oxygen species (ROS) levels. Furthermore, the depletion of αSnap in ISCs promotes the expression of Calr, Prtp, LRP1 and Mcr, which might function downstream of αSnap in regulating the survival of ISCs. In addition, we demonstrated that deficiency of Napa (αSnap homologue in mice) restricts the development of mouse GL261 glioma cell transplantation tumor and induces a senescence cascade in GL261 tumor cells. Overall, these findings indicate that αSnap could serve as a potential therapeutic target for glioma.