The Hispaniolan solenodon, Solenodon paradoxus, and Hispaniolan hutia, Plagiodontia aedium, are the Dominican Republic’s only surviving endemic non-volant land mammals, and are high priorities for conservation. The country has an extensive protected area (PA) network designed to maintain habitats and benefit biodiversity, but which faces significant anthropogenic threats likely to detrimentally impact both species. We examined how differences in habitats, forest structure, topography and human activity influence presence of solenodons and hutias across the Dominican Republic. Systematic surveys of seven PAs were undertaken to record indirect signs, with presence-absence data analyzed using a multi-model inference approach incorporating ecological variables from both field and GIS data. Solenodons were detected relatively frequently, whereas detections of hutias were uncommon. Lower elevations, increased surrounding tree cover, canopy closure, and reduced levels of low vegetation are all associated with increased probability of detecting solenodons, whereas agriculture and mangrove represent poor-quality habitat. Increased canopy closure, tree basal area (indicating older-growth forest), and increased rock substrate (providing more den sites) are associated with increased probability of detecting hutias. Our findings indicated that human activities within PAs are likely to negatively affect both species, and conservation activities should focus on preventing encroachment and conversion of forest to agriculture to maintain high-quality forest habitats.