Trehalose-6-phosphate phosphatase (TPP) has been regarded as one major enzyme that is directly involved in the synthesis of trehalose. The function of TPP families has been demonstrated to be related to various biological processes in higher plant species. In this study, a total of 10 members of the TPP family have been identified in the assembly of cassava (Manihot esculenta). The annotation and chromosomal distribution of the MeTPP genes have been obtained. We found that the MeTPP genes are randomly localized in the chromosomes. Particularly, chromosome 2, 6 and 14 share the highest members (2) of the MeTPP family. Analysis of the 1000 bp sequences in the promoter regions of the MeTPP gene family showed a distribution of phytohormone- responsive cis- regulatory elements. Particularly, the promoter regions of 8 MeTPP genes contain at least one cis- regulatory elements that are responsive to auxin, ethylene, abscisic acid, salicylic acid, jasmonic acid and gibberellin. Of our interest, our RNA-Seq analysis indicated that 7 MeTPP genes are expressed in at least one major organ/tissue. Interestingly, MeTPP09 is specifically expressed in leaf, mid vein samples and highly expressed in stem, somatic organized embryogenic structure and root apical meristem samples, while two genes, like MeTPP03 and 05 are tended to highly expressed in friable embryogenic callus samples. The results of this study could provide comprehensive information of the TPP family in cassava for further functional characterization of the MeTPP genes related to stress tolerance.