Salinity stress is one of the most important abiotic stresses that causes great losses in crop production worldwide. Identifying the molecular mechanisms of salt resistance in sorghum will help develop salt-tolerant crops with high yields. Sorghum (Sorghum bicolor (L.) Moench) is one of the world’s four major grains and is known as a plant with excellent adaptability to salt stress. Among the various genotypes of sorghum, a Korean cultivar Nampungchal is also highly tolerant to salt. However, little is known about how Nampungchal responds to salt stress. In this study, we measured various physiological parameters, including Na⁺ and K⁺ contents, in leaves grown under saline conditions and investigated the expression patterns of differentially expressed genes (DEGs) using QuantSeq analysis. These DEG analyses revealed that genes up-regulated in a 150 mM NaCl treatment have various functions related to abiotic stresses, such as ERF and DREB. In addition, transcription factors such as ABA, WRKY, MYB, and bZip bind to the CREs region of sorghum and are involved in the regulation of various abiotic stress-responsive transcriptions, including salt stress. These findings may deepen our understanding of the mechanisms of salt tolerance in sorghum and other crops.