The stable maintenance of genomic integrity is essential for the survival of a species. Among the various cell types in multicellular organisms, germ cells are particularly important, serving as carriers that transmit genetic information to the next generation through meiosis and fertilization. Using Drosophila melanogaster as a model, we have demonstrated that RNA silencing—driven by small non-coding RNAs (20–30 nucleotides in length)—plays a central role in safeguarding the genome in germ cells and preserving reproductive capacity. Moving forward, we aim to extend our research to mammalian germ cells to unravel the complex regulatory mechanisms of RNA silencing and its influence on the epigenome, through a combination of biochemical and computational approaches.