Cancer-related mortality is highest among colorectal cancer patients, and understanding its molecular mechanisms is essential to developing effective treatments. In this study, we performed RNA sequencing (RNA-seq) analysis of a total 376 normal colon and CRC samples. CRC fresh-frozen tissues and adjacent normal tissue samples were archived from Seoul National University Hospital, South Korea to investigate difference in the biology characteristics between normal and cancer tissues. A total of 58,380 genes were expressed in both CRC tissue and normal tissue. According to functional annotation analysis, upregulated genes in tumor were significantly enriched in pathways related to cell cycle, MAPK pathway and cancer-related ECM signaling, while genes highly expressed in normal tissues were enriched mainly in metabolic pathways. A Consensus Molecular Subtype (CMS) analysis was also performed to determine the relationship between the clinical information and subtypes. These findings provide valuable insights into the molecular mechanisms underlying Korean CRC patients and suggest potential targets for new treatments. Finally, raw files and processed data used to generate results in this paper were deposited into a public repository for further exploration.