Halophytic plant Lycium ruthenicum Murr. is widely distributed in salinized desert of Qinghai-Tibet Plateau. The molecular regulatory network of L. ruthenicum tolerance to salt stress remains unclear. In this study, RNA-seq transcriptomes derived from leaf, stem, and root of seedling treated with 0 or 200 mM NaCl were investigated. The content of anthocyanin and superoxide dismutase activity in stem was significantly up-regulated when compared to control. Multiple peroxidase genes were up-regulated in stem although its enzymatic activity enhanced but not in a significant level. Of 1818, 1171, and 1427 differentially expressed genes (DEGs) in salt-treated roots, stems, and leaves were respectively identified when compared to control. According to the DEGs mentioned above, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the flavonoid biosynthesis was commonly enriched in salt-treated root, stem, leaf. A salt stress-modulated regulatory network was constructed using weighted correlation network analysis, which predicted MYB transcription factor MYBHG19192 co-expressing with reactive oxygen species scavenging genes, anthocyanin biosynthetic genes, abscisic acid and ethylene signaling genes, and Salt Overly Sensitive (SOS) signaling genes. Dual-luciferase reporter assay verified that MYBHG19192 promote the expression of anthocyanin glucosyltransferase gene UF3GTHG27071 and SOS signaling gene SOS3HG03260, suggesting that the regulatory network presented here indeed function, partially if not completely, in seedling tolerance to salt stress. In sum, the genome-scale transcriptome provide valuable resource for globally uncovering the molecular mechanism underlying of seedling tolerance to salt stress and the hub gene MYBHG19192 will be a key gene for genetic improvement of L. ruthenicum.