Components of the SWI/SNF chromatin-remodeling complex are among the most frequently mutated genes in various human cancers, yet only SNF5, a core member of the SWI/SNF chromatin-remodeling complex, is found mutated in malignant rhabdoid tumors (MRTs), which are primarily found in young children. How SNF5 functions differently from other members of the SWI/SNF complex remains unclear. Here we use Drosophila imaginal epithelial tissues to demonstrate that Snr1, the conserved homolog of human SNF5 (hSNF5), prevents tumorigenesis by ensuring normal endosomal-trafficking-mediated signaling cascades. We show that disruption of snr1 causes massive apoptosis in the wing pouch area and obvious overgrowth in the notum region of imaginal discs. Blocking apoptosis by coexpression of the anti-apoptotic protein p35 in snr1-knockdown cells results in neoplastic tumorigenic overgrowth in imaginal epithelial tissues, whereas depletion of any other members of the SWI/SNF complex does not induce similar phenotypes. The snr1-knockdown-induced tumors show multiple hallmarks of cancer, including sustained proliferation, altered metabolism, and dedifferentiation. Unlike other components of the SWI/SNF complex which are only detected in the nucleus, Snr1 is observed in both the nucleus and the cytoplasm. The cytoplasmic function of Snr1 is probably necessary for endosomal trafficking, because components of the trafficking signaling pathway are enriched in snr1-depleted cells and transmembrane proteins are accumulated in the cell surface. Further experiments demonstrate that aberrant regulation of multiple signaling pathways, including Notch, JNK, and JAK/STAT is responsible for snr1-loss-of-function-mediated tumor progression. RNA profiling of snr1-depleted tumors by RNA-Seq analysis confirms that, indeed, several signaling targets are transcriptionally degregulated. Our data provide an alternative way to understand the mechanism of how hSNF5 suppresses MRTs during early childhood. The detailed results will be presented in the 57th Annual Drosophila Research Conference @TAGC.