The genus Hexasepalum (Rubiaceae) is the priority name for Diodella and was recently re-established over the latter taxon. In this study we describe Hexasepalum nordestinum, a new species from northeast Brazil, which occurs in extremely fragmented areas of Ceará and Piauí states and is assessed here as endangered. The new species is compared with its closest relatives and the first taxonomic key to distinguish all species of Hexasepalum from the Americas is presented. A description, illustrations including electron microphotographs of the fruits, seeds, and pollen grains, and details of habitat, ecology, and an evaluation of conservation status are provided.