Abstract: Objective：To analyze the genomic differences between tumor and peritumoral tissues of patients with colon cancer associated with inflammatory bowel disease. Methods：We collected formalin fixed and paraffin embedded tissues (FFPE) from 3 patients who were diagnosed as colorectal cancer during long-term follow-up of inflammatory bowel disease. They underwent surgical resection from January 2016 to June 2016 and were diagnosed as colon cancer complicated with Crohn’s disease or ulcerative colitis pathologically. The tumor tissue and the adjacent peritumoral tissues were sequenced using Illumina Hiseq platform. Then we analyzed the gene expression difference and carried out the Pathway function classification and enrichment analysis. Differential gene validation was performed in animal tissues of inflammatory bowel cancer model. Results：The quantity and quality distribution of base content in FFPE specimens within six months after filtration were consistent with the requirements of statistical analysis, and the data between samples were comparable. The results showed that the different genes between tumor tissue and peritumoral tissue were mainly focused on autoimmune diseases, infectious diseases, and signal transduction. The primary immunodeficiency related pathways were mostly involved. Conclusions：The development of colon cancer associated with inflammatory bowel disease is most closely related to immunodeficiency, followed by infection and signal transduction.