Deperetellidae is a clade of peculiar, Asian endemic tapiroids from the early and middle Eocene. The previously published material mainly comprises maxillae, mandibles, and some postcranial elements. However, the absence of cranial materials and primitive representatives of the deperetellids obscures their phylogenetic relationships within Tapiroidea. Furthermore, derived deperetellids have completely molarized premolars, but the pattern of their evolution remains unclear. Here, we report a nearly complete skull and some carpals of a new basal deperetellid tapiroid, Irenolophus qii gen. et sp. nov., from the late early Eocene of the Erlian Basin, Inner Mongolia, China. We suggest that deperetellids (along with Tapiridae) probably also arose from some basal ‘helaletids’, based on the reduced, flat, lingually depressed metacones on the upper molars, the trend towards the bilophodonty on the lower molars, and a shallow narial notch with the premaxilla in contact with the nasal. The molarization of the premolars in Deperetellidae from Irenolophus through Teleolophus to Deperetella was initiated and gradually enhanced by the separation between the paraconule and the protocone. That pattern differs from the protocone-hypocone separation in helaletids, tapirids, and most rhinoceroses, and the metaconule-derived pseudohypocone in amynodontids. However, the specific relationship of deperetellids within Tapiroidea and the roles of different patterns of premolar molarization in perissodactyl evolution need further and comprehensive study.