Salinity adversely affects growth and yield of crop plants. Plants respond to salinity using a series of physiological and biochemical mechanisms through an orchestrated regulation of many genes. Halophyte species have attracted attention of plant biologists to explore their salinity tolerance mechanisms. This knowledge may provide novel routes to improve salinity stress tolerance in crop plants resulting in higher sustainable yields. Salicornia persica is an Iranian native halophyte species that can tolerate extreme salinity. We performed Illumina high-throughput RNA sequencing and functional annotation on shoots of S. persica under control and salinity conditions to investigate the molecular mechanisms controlling salinity adaptation in this halophyte. Over 68 million and 65 million clean reads were generated from control and salinity-treated libraries, respectively. We identified 1595 differentially expressed genes including several transcription factors, protein kinases and transporters. Functional annotation analysis suggested that energy homeostasis and synthesis of primary metabolites play key roles for salinity adaptation in S. persica. Furthermore, gene network analysis indicated that abscisic acid and calcium signaling as well as sodium compartmentalization are major components to confer tolerance to salinity in S. persica. This first report on transcriptome analysis of the halophyte S. persica provided insight into the mechanisms underlying salinity tolerance and served as a platform for future studies.