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Transgene silencing is a common phenomenon observed in , particularly in the germline, but the precise mechanisms underlying this process remain elusive. Through an analysis of the transcription factors profile of , we discovered that the expression of several transgenic reporter lines exhibited tissue-specific silencing, specifically in the intestine of . Notably, this silencing could be reversed in mutants defective in endogenous RNA interference (RNAi). Further investigation using knock-in strains revealed that these intestine-silent genes were indeed expressed , indicating that the organism itself regulates the intestine-specific silencing. This tissue-specific silencing appears to be mediated through the endo-RNAi pathway, with the main factors of this pathway, and , are significantly enriched in the intestine. Additionally, histone modification factors, such as , are involved in this silencing mechanism. Given the crucial role of the intestine in reproduction alongside the germline, the transgene silencing observed in the intestine reflects the self-protective mechanisms employed by the organisms. In summary, our study proposed that compared to other tissues, the transgenic silencing of intestine is specifically regulated by the endo-RNAi pathway.