The proper accumulation and maintenance of stem cells is critical for organ development and homeostasis. The Notch signaling pathway maintains stem cells in diverse organisms and organ systems. In <i>Caenorhabditis elegans</i>, GLP-1/Notch activity prevents germline stem cell (GSC) differentiation. Other signaling mechanisms also influence the maintenance of GSCs, including the highly-conserved TOR substrate ribosomal protein S6 kinase. Although <i>C. elegans</i> bearing either a null mutation in <i>
rsks-1</i>/S6K or a reduction-of-function (<i>rf</i>) mutation in <i>
glp-1</i>/Notch produce half the normal number of adult germline progenitors, virtually all these single mutant animals are fertile. However, <i>
glp-1(rf)</i><i>
rsks-1(null)</i> double mutant animals are all sterile, and in about half of their gonads, all GSCs differentiate, a distinctive phenotype associated with a significant reduction or loss of GLP-1 signaling. How <i>
rsks-1</i>/S6K promotes GSC fate is unknown. Here, we determine that <i>
rsks-1</i>/S6K acts germline-autonomously to maintain GSCs, and that it does not act through Cyclin-E or MAP kinase in this role. We found that interfering with translation also enhances <i>
glp-1(rf)</i>, but that regulation through <i>
rsks-1</i> cannot fully account for this effect. In a genome-scale RNAi screen for genes that act similarly to <i>
rsks-1</i>/S6K, we identified 56 RNAi enhancers of <i>
glp-1</i>/Notch sterility, many of which were previously not known to interact functionally with Notch. Further investigation revealed six candidates that, by genetic criteria, act linearly with <i>
rsks-1</i>/S6K. These include genes encoding translation-related proteins, <i>
cacn-1</i>/Cactin, an RNA exosome component and a Hedgehog-related ligand. We found that additional Hedgehog-related ligands may share functional relationships with <i>
glp-1</i>/Notch and <i>
rsks-1</i>/S6K in maintaining germline progenitors.