Background Drought and salinity are two of the main challenges in agriculture. In many areas, crop production needs solutions to adapt the grown species to the increasing salinity. Research on physiological and molecular responses activated by salinity in plants is needed to elucidate mechanisms of salinity tolerance. Transcriptome profiling (RNA-Seq) is a powerful tool to study the transcriptomic profile of genotypes under stress conditions. In temperate fruit tree species, tree grafting on salinity tolerant rootstocks is a common method to compensate for the cultivar saline sensitivity. Persimmon species have different levels of tolerance to salinity, knowledge of this variability provides the basics for development of salt tolerant rootstocks.Results In this study, we conducted a physiological and transcriptomic profiling of roots and leaves in tolerant and sensitive plants of persimmon rootstock, Diospyros lotus, grown under saline and control conditions. Results from characterization of the physiological responses along with gene expression changes in roots and leaves allowed identifying several salt-tolerance mechanisms related to Ion transport and thermospermine synthesis. Differences were observed in putative H+/ATPases that allow transmembrane ionic transport and Chloride channel protein-like genes. Furthermore, an overexpression of thermospermine synthase found in the roots of tolerant plants may indicate that alterations in root architecture could act as an additional mechanism of response to salt stress. Conclusions Results indicate that D. lotus presents a genetic variability for salt tolerance trait related to the regulation of chloride transport, transmembrane electrochemical potential and thermospermine root synthesis. The study provides knowledge on mechanism of salt stress tolerance in persimmon for further breeding of tolerant persimmon rootstocks.