Colorectal cancer (CRC) is a common tumor in digestive system with high morbidity and mortality. In this work, three datasets (GSE68468, GSE21510, and GSE9348) were selected from the public GEO database, and the deferentially expressed genes (DEGs) related to CRC were screened out by bioinformatics approach. The GO (gene ontology) analysis on DEGs was carried out and followed by the KEGG (kyoto encyclopedia of genes and genomes) analysis. Finally, protein-protein interaction (PPI) networks of DEGs were respectively constructed by using the STRING database. Our results showed that a total of 849 DEGs in common were identified from the three datasets, including 406 up-regulated genes and 443 down-regulated genes. The GO analysis demonstrated that the DEGs are mainly related to cell division, cell proliferation, cell signaling, and immune response. The KEGG analysis revealed that DEGs are mainly enriched in cell cycle and cell signaling pathway. Based on the PPI network analysis, we identified a total of 86 key genes: 72 up-regulated genes mainly consist of CD and KIF genes while 14 down-regulated genes are mainly composed of various members of CC genes. In particular, we found that the CRC proliferation should be enhanced by the interaction of CDK1 with CDKN3 and KIF15. On the one hand, CRC proliferation is enhanced by over-expressing the CD and KIF genes involving in cell division and cell proliferation. On the other hand, CRC proliferation is strengthened through silencing the expression of the CC genes associated with immune response.