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Summary: Animal reproduction responds to nutritional status. During starvation, Drosophila and Caenorhabditis elegans enter a period of reproductive diapause with increase apoptosis, while maintaining a stable pool of germline stem cells (GSCs). How GSCs are protected is not understood. Here, we show that a sisRNA/miRNA axis maintains ovarian GSCs during starvation in Drosophila. Starvation induces the expression of an ovary-enriched sisRNA sisR-2, which negatively regulates GSC maintenance via a fatty acid metabolism gene dFAR1. sisR-2 promotes the expression of bantam, which in turn inhibits the activity of sisR-2, forming a negative feedback loop. Therefore, bantam acts as a buffer to counteract sisR-2 activity to prevent GSC loss during starvation. We propose that the sisR-2/bantam axis confers robustness to GSCs in Drosophila. : Osman and Pek report a novel regulatory axis between a sisRNA and a miRNA, which protects germline stem cells (GSCs) from loss during starvation in Drosophila. The starvation-induced sisRNA, sisR-2, represses GSC maintenance via a fatty acid metabolism gene dFAR1. bantam negatively feedbacks to sisR-2, acting as a buffer to counteract sisR-2 activity, preventing GSC loss during starvation. Keywords: Drosophila, sisRNA, miRNA, germline stem cell, starvation, bantam, homeostasis, feedback, robustness