The body louse has the smallest genome size among the known genome-sequenced insects. Here, 81 GPCRs were identified in Pediculus humanus humanus, 56, 14, 6 and 5 GPCRs for family-A, -B, -C and -D, respectively. These GPCRs constitute the comparable repertoire of GPCRs with other insects. Moreover, it contains a more complete set of neuropeptide and protein hormone receptors not even than Acyrthosiphon pisum but also Drosophila melanogaster, for example, Sulfakinin, Corazonin, Trissin and PTHRL only presented in P. h. humanus but lost either in A. pisum or D. melanogaster. However, it has less duplication among the sub-families. Meanwhile, ACP, AVPL, HE6 receptors and Boss were also absent from P. h. humanus. These results indicated that the repertoire of GPCRs in P. h. humanus were not affected by its smallest genome size, and further suggested that P. h. humanus has a relatively original and concise GPCR regulation system.