Stress induced by low temperature, which represents a widespread environmental factor,strongly affects maize growth and yield. However, the physiological characteristics and molecular regulatory mechanisms of maize seedlings in response to cold remain poorly understood. In this study, using RNA-seq, we investigated the transcriptome profiles of two sweet com inbred lines, “Richao”(RC) and C5, under cold stress. A total of 357 and 455 differentially expressed genes(DEGs) were identified in the RC and C5 lines, respectively, 94 DEGs were detected as common DEGs related to cold response in both genotypes, and a total of 589 DEGs were detected as cold tolerance-associated genes. By combining protein function clustering analysis and significantly enriched Gene Ontology(GO) terms analysis,we suggest that transcription factors may play a dominating role in the cold stress response and tolerance of sweet com. Furthermore, 74 differentially expressed transcription factors were identified, of those many genes involved in the metabolism and regulation of hormones. These results expand our understanding of the complex mechanisms involved in chilling tolerance in maize, and provide a set of candidate genes for further genetic analyses. However, the physiological characteristics and molecular regulatory mechanisms of maize seedlings in response to cold remain poorly understood. In this study, using RNA-seq, we A total of 357 and 455 differentially expressed genes (DEGs) were identified in the RC and C5 lines, respectively, 94 DEGs were detected as common DEGs related to cold response in both genotypes, and a total of 589 DEGs were detected as cold tolerance-associated genes. By combining protein function clustering analysis and significantly enriched Gene Ontology (GO) terms analysis, we suggest that transcription factors may play a dominating role in the cold stress response and tolerance of sweet com. of, 74 differentially expressed transcription factors were identified, of these many genes involved in the metabolism and regulation of hormones. These results expand our understanding of the complex mechanisms involved in chilling tolerance in maize, and provide a set of candidate genes for further genetic analyzes.