Abstract： Objective To explore the relationship between colorectal cancer and obesity,and to provide insight into the patho-genesis of colorectal cancer.Methods Differential expression genes(DEGs)and obesity-related genes were screened from TCGA and GeneCards databases,and the co-expressed genes were obtained by Venn diagram.Functional enrichment analysis of co-expressed genes was performed using DAVID database.According to the protein-protein interaction(PPI)network diagram constructed by STRING database and Cytoscape software,10 key genes were selected and 3 key hub genes were obtained after intersection.Finally,the data set GSE39582 in GEO database was verified,and the information of colorectal cancer clinical samples in TCGA database was used for survival analysis.Results 33 coexpressed genes were obtained after the intersection of differential genes and obesity-related genes in colorectal cancer.The results of functional enrichment analysis showed that they may be related to the activity of hormones and extra-cellular space.The three key genes screened by PPI analysis were PYY,SLC2A4 and SERPINE1.As verified by GSE39582 dataset,the expression levels of 3 hub genes in colorectal cancer samples were significantly different from those in normal control samples(P<0.05).Survival analysis showed that high SERPINE1 expression was negatively correlated with overall survival of colorectal cancer(P<0.05).Conclusion The three key genes screened in this study may affect the occurrence and development of colorectal cancer through obesity-related pathways.