Division of labor is a distinguishing characteristic of eusocial insects. To understand the proximate factors underlying caste determination, it is essential to clarify the developmental mechanisms during the differentiation of each caste. Termite soldiers have species-specific and diverse morphologies that are specialized for colony defense. Soldiers of the subfamily Nasutitermitinae (Termitidae), one of the most derived termite groups, possess a long, horn-like frontal projection (nasus), an invaginated glandular structure in the head (frontal gland), and regressed mandibles. These morphological changes occur prior to the molt into presoldiers (the preceding stage of soldiers). In Drosophila and other insects, Hox genes determine segment identities; thus they might be involved in such body-part-specific modifications during soldier differentiation. Deformed (Dfd) functions not only in the formation of the mandible and maxilla but also in other head parts (e.g., eye-antennal disc) in other insects. In this study, we examined Dfd functions in nasus/frontal gland formation and mandibular regression in Nasutitermes takasagoensis. Relative expression analyses showed that Dfd expression levels in the mouthparts were significantly higher than those in any other body parts of workers before presoldier molt. Dfd RNA interference resulted in the inhibition of mandibular regression during presoldier differentiation, but nasus and frontal gland formation were not affected. These results suggest that Dfd is involved in the determination of mandibular positional information and specific modification during presoldier differentiation in N. takasagoensis. This is the first work to show the effects of Hox genes on caste-specific morphogenesis in social insects. J. Exp. Zool. (Mol. Dev. Evol.) 320B: 385–392, 2013. © 2013 Wiley Periodicals, Inc.