Microbes, commensals, and pathogens, control the numerous functions in the host cells. They can alter host signaling and modulate immune surveillance by interacting with the host proteins. For shedding light on the contribution of microbes to health and disease, it is vital to discern how microbial proteins rewire host signaling and through which host proteins they do this. Host-Microbe Interaction PREDictor (HMI-PRED) is a user-friendly web server for structural prediction of protein-protein interactions (PPIs) between the host and a microbial species, including bacteria, viruses, fungi, and protozoa. HMI-PRED relies on “interface mimicry” through which the microbial proteins hijack host binding surfaces. Given the structure of a microbial protein of interest, HMI-PRED will return structural models of potential host-microbe interaction (HMI) complexes, the list of host endogenous and exogenous PPIs that can be disrupted, and tissue expression of the microbe-targeted host proteins. The server also allows users to upload homology models of microbial proteins. Broadly, it aims at large-scale, efficient identification of HMIs. The prediction results are stored in a repository for community access. HMI-PRED is free and available at https://interactome.ku.edu.tr/hmi. Display omitted •HMI-PRED is a user-friendly web server for host-microbe interaction prediction.•HMI-PRED relies on interface mimicry—the hijacking of host protein binding surfaces.•Any microbial proteins, both pathogenic and commensal proteins, can be analyzed.