Although it is clear that intracellular pathogens use a variety of secreted and surface proteins to interact with and manipulate their hosts, a systematic approach for identifying such proteins has been lacking. Because of this, the identity of these host-exposed proteins is often unknown in many pathogens. Additionally, little is known about how conserved repertoires of host-exposed proteins are between related species. Microsporidia are a large phylum of eukaryotic obligate intracellular parasites that can specifically infect a variety of different animal species. To identify host-exposed proteins from microsporidia, we used spatially restricted enzymatic tagging followed by mass spectrometry on C. elegans infected with two related species of Nematocida microsporidia. Using this approach, we identified 82 microsporidia proteins that are exposed inside of host intestinal cells, including several in the nucleus. These proteins are enriched in targeting signals, lack conservation with other microsporidia species, are rapidly evolving, and lack domains with known function. Almost half of the identified proteins belong to large, Nematocida-specific gene families that are undergoing species-specific radiations. We also find that large, species-specific families with targeting signals are common throughout microsporidia species. Our data suggest that the use of a large number of rapidly evolving species-specific proteins represent a common strategy for these intracellular pathogens to interact with their hosts.