Abstract: RNase is a kind of RNA hydrolase that widely exists in organisms. RNase T2 in plants functions by hydrolyzing and processing RNA in the cell. However, the mechanism by which RNase T2 acts on intercellular RNA to exert the resistance function has not been studied. Here, we identified the S-like RNase TaRNS4 that positively regulates wheat resistance to stripe rust by degrading the RNA of Puccinia striiformis f. sp. tritici (Pst), the causative agent of stripe rust. Importantly, TaRNS4 phosphorylation mediated by receptor-like kinase TaRLK5 contributes to its degradation of Pst RNA and enhances plant resistance, and changes in a single active site can significantly reduce RNA degradation efficiency. However, the serine/threonine protein phosphatase TaPP2C10 can bind to TaRNS4 and dephosphorylate it to inhibit Pst RNA degradation to promote Pst colonization. Meanwhile, it was found that TaPP2C10, as a negative regulator, can also increase plant susceptibility by binding to TaMAPK6 and dephosphorylating it. Moreover, TaRNS4 was found to increase wheat resistance to Pst by hijacking TaPP2C10 to relieve its dephosphorylation of TaMAPK6. Overall, these findings indicate that the TaRNS4–TaPP2C10 module fine-tunes plant immunity in an antagonistic manner and highlight the versatility of TaRNS4, which enhances plant resistance by synergizing RNA degradation and the MAPK cascade.