potato (Solanum tuberosum L.) is an important staple food worldwide. However, its growth has been heavily suppressed by salt stress. The molecular mechanisms of salt tolerance in potato remain unclear. It has been shown that the tetraploid potato Longshu No. 5 is a salt-tolerant genotype. Therefore, in this study we conducted research to identify salt stress response genes in Longshu No. 5 using a NaCl treatment and time-course RNA sequencing. The total number of differentially expressed genes (DEGs) in response to salt stress was 5508. Based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, it was found that DEGs were significantly enriched in the categories of nucleic acid binding, transporter activity, ion or molecule transport, ion binding, kinase activity and oxidative phosphorylation. Particularly, the significant differential expression of encoding ion transport signaling genes suggests that this signaling pathway plays a vital role in salt stress response in potato. Finally, the DEGs in the salt response pathway were verified by Quantitative real-time PCR (qRT-PCR). These results provide valuable information on the salt tolerance of molecular mechanisms in potatoes, and establish a basis for breeding salt-tolerant cultivars. Salt is a major abiotic factor affecting plant growth and secondary metabolism 1. Soil salinization has become a global problem with about 8 × 10 8 hectares of soil worldwide threatened by salinization 2. Salinity interferes with plant growth as it leads to physiological drought and ion toxicity 3. In addition, other secondary stresses, such as oxidative damage, can occur in plants subjected to high NaCl concentrations 1. With the increase of salinization, it is a tough challenge to increase grain output and achieve food security. Potato (Solanum tuberosum L.) is an extremely important food staple worldwide due to its versatility and nutritional value. However, potato is quite sensitive to salt stress, which is one of the most important factors limiting its cultivation 4 and which can lead to serious declines in yield 5,6. Therefore, there is a great need to improve the salt tolerance of potato and breed salt-tolerant varieties. What's more, illuminating the molecular mechanisms underlying salt tolerance and identifying the related genes of tolerant plants may contribute to further understanding the functions of these unique genes. Previous studies have revealed mechanisms underlying salt stress tolerance in plants. Plant membrane receptors sense extracellular salt stress stimuli, and then these stimuli signals are translated into intracellular signals through the generation of second messengers such as calcium, reactive oxygen species (ROS) and inositol phosphates. These second messengers then activate transcription factors (TFs) or protein kinases (PKs), inducing specific genes to be differentially expressed 7. These signal cascades result in the expression of multiple stress-responsive genes, the products of which can directly or indirectly confer s...