Sweetpotato is the seventh important food crop in the world. Although sweet potato is widely adaptable to unfavorable conditions such as drought and high salt, this species originating from tropical region remains low-temperature sensitive. In this study, cold-tolerant sweet potato variety “Liaoshu 36” was subjected for cold-stress treatments at 0 h, 6 h, 24 h and 48 h, and total RNAs were sampled for the transcriptome sequencing analysis. The results showed that 75.01 Gb transcriptome data were produced, and 76.33% of them were mapped to the reference genome. The differentially expressed gene (DEG) analysis revealed 6282 up-regulated genes were and 3881 down-regulated genes. Co-expression patterns analysis showed that 283 genes were up-regulated and 26 genes were down-regulated at all three treatments (6 h, 24 h, and 48 h). GO enrichment analysis showed that DEGs were mainly enriched on seven categories: protein kinase activity, peroxidase activity, oxidoreductase activity, protein phosphorylation, amino acid transmembrane transport, protein-chromophore linkage and pectin catabolic process. KEGG pathway enrichment showed that DEGs involved in phenylpropanoid biosynthesis, starch and sucrose metabolism, plant hormone signal transduction, plant-pathogen interaction, glutathlone metabolism. Moreover, four key genes (PYL, PP2C, SnRK2 and ABF) in ABA signal transduction pathway were identified to be closely related to low temperature stress response, which provided theoretical basis for the cloning of sweet potato chilling tolerance genes and the analysis of cold tolerance mechanism.