Thellungiella salsuginea is highly tolerant to abiotic stress, while its a close relative Arabidopsis thaliana is sensitive to stress. This characteristic makes T.salsuginea an excellent model for uncovering the mechanisms of abiotic stress tolerance. Abscisic acid (ABA) plays essential roles in plant abiotic and biotic stress tolerance. To test the changes in gene expression of T.salsuginea under ABA treatment, in this study, the transcriptomes of T.salsuginea roots and leaves were compared in response to exogenously application of ABA. The results showed that ABA treatment caused different expression of 2,200 and 3,305 genes in leaves and roots, respectively, compared with the untreated control. In particular, genes encoding transcription factors such as WRKY, MYB, NAC, GATA, ethylene-responsive factors (ERFs), heat stress transcription factors, basic helix-loop-helix, PLATZ and B3 domain-containing family members were enriched. In addition, 49 and 114 differentially expressed genes were identified as ABA-regulated genes, separately in leaves and roots, respectively, which were related to biotic and abiotic stresses. The expression levels of some genes were validated by qRT-PCR. Different responses of genes to ABA treatment were discovered in T.salsuginea and A.thaliana. This transcriptome analysis expands our understanding of the role of ABA in stress tolerance in T.salsuginea. Our study provides a wealth of information for improving stress tolerance in crop plants.