BACKGROUND: Colorectal cancer is the third most common cancer worldwide and one of the leading causes of cancer-related death. However, current treatment options are not ideal. METHODS: In this study, mRNAs, lncRNAs, and circRNAs expression profiles in four pairs of HCT116 and FHC cells were detected by microarray technology. The potential functions and enriched pathways of the differentially expressed RNAs were predicted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analyses. Bioinformatics software was used to construct co-expression networks of lncRNA-miRNA-mRNA and circRNA-miRNA to reveal the potential mutual regulatory mechanisms of ceRNA. RESULTS: The result showed that 6681 mRNAs, 12784 lncRNAs, and 14301 CircRNAs were changed in HCT116 and FHC groups. Meanwhile, the differentially expressed RNAs were confirmed by RT-qPCR and then focused on the up-regulated genes of hsa_circ_0025288, ENSG00000233429.9, and NT5E by Maximum difference expression level. CONCLUSION: This study provides a theoretical basis for the regulatory mechanism of non-coding RNAs in the pathogenesis and development of colorectal cancer cells. Therefore, this study pointed to ENSG00000233429.9 and hsa_circ_0025288 as potential molecular targets for colorectal cancer treatment in the future.