Pomegranate (Punica granatum L.) is widely grown in arid and semi-arid soils, with constant soil salinization. To elucidate its molecular responses to salt stress on mRNA levels, we constructed 18 cDNA libraries of pomegranate roots and leaves from 0 (controls), 3, and 6 days after 200 mM NaCl treatment. In total, we obtained 34,047 genes by mapping to genome, and then identified 2255 DEGs (differentially expressed genes), including 1080 up-regulated and 1175 down-regulated genes. We found that the expression pattern of most DEGs were tissue-specific and time-specific. Among root DEGs, genes associated with cell wall organization and transmembrane transport were suppressed, and most of metabolism-related genes were over-represented. In leaves, 41.29% of DEGs were first suppressed and then recovered, including ions/metal ions binding-related genes. Also, ion transport and oxidation-reduction process were restricted. We found many DEGs involved in ABA, Ca2+-related and MAPK signal transduction pathways, such as ABA-receptors, Ca2+-sensors, MAPK cascades, TFs, and downstream functional genes coding for HSPs, LEAs, AQPs and PODs. Fifteen genes were selected to confirm the RNA-seq data using qRT-PCR. Our study not only illuminated pomegranate molecular responses to salinity, but also provided references for selecting salt-tolerant genes in pomegranate breeding processes.