Trans-kingdom RNA plays a key role in host-parasite interactions. Hosts export specific endogenous microRNAs (miRNAs) into pathogens to target pathogen virulence genes and inhibit their invasion. In addition, trans-kingdom sRNAs produced by parasites may function as RNA effectors to suppress host immunity. Here, we summarize recent, important findings regarding trans-kingdom RNA and focus on the roles of trans-kingdom RNA in driving an evolutionary arms race between host and pathogen. We suggest that trans-kingdom RNA is a new platform for such arms races. Furthermore, we conjecture that trans-kingdom RNA contributes to horizontal gene transfer (HGT) involved in host-pathogen interactions. In addition, we propose that trans-kingdom RNA exchange and RNA driven HGT can have a great impact on the evolutionary ecology of interacting species.