Intragenomic conflicts are fueled by rapidly evolving selfish genetic elements, which induce selective pressures to innovate opposing repressive mechanisms. This is patently manifest in sex-ratio (SR) meiotic drive systems, in which distorter and suppressor factors bias and restore equal transmission of X and Y sperm. Here, we reveal that multiple SR suppressors in Drosophila simulans (Nmy and Tmy) encode related hairpin RNAs (hpRNAs), which generate endo-siRNAs that repress the paralogous distorters Dox and MDox. All components in this drive network are recently evolved and largely testis restricted. To connect SR hpRNA function to the RNAi pathway, we generated D. simulans null mutants of Dcr-2 and AGO2. Strikingly, these core RNAi knockouts massively derepress Dox and MDox and are in fact completely male sterile and exhibit highly defective spermatogenesis. Altogether, our data reveal how the adaptive capacity of hpRNAs is critically deployed to restrict selfish gonadal genetic systems that can exterminate a species. Display omitted •Selfish sex ratio (SR) distorters impede son transmission and must be silenced•Multiple SR suppressors in Drosophila simulans correspond to hairpin RNA-siRNA loci•Knockout of RNAi pathway derepresses SR drivers and disrupts spermatogenesis•Rapidly evolving intragenomic conflicts and suppression by RNAi may underlie speciation Lin and Hu et al. reveal a critical biological usage of RNAi in Drosophila simulans to tame meiotic drive systems. Multiple autosomal hairpin-siRNA loci are deployed to suppress X-encoded distorter loci that bias progeny sex ratio. These loci are rapidly evolving and testis restricted, and such intragenomic conflicts may fuel speciation.