Background: Studies highlight the role of migrasomes as mediators of intercellular communication and signaling, critical in influencing tumorigenesis and progression. Yet migrasome-related genes and their potential role in colorectal cancer prognosis remain unexplored. Methods: Differentially expressed gene set A (DEG set A) was identified in the TCGA-CRC dataset, and Weighted Gene Co-expression Network Analysis (WGCNA) was performed to identify the most important modules associated with migrasome-related gene (MRG) scores. Single-cell RNA-seq dataset GSE231559 DEG set B was determined. Candidate migrasome-related genes were filtered by intersecting DGE set A, key module genes, and DEG set B. Prognostic genes were subsequently screened through regression analysis, and a risk model was developed. Patients with CRC in the TCGA cohort were stratified into high- and low-risk groups based on the optimal cutoff of the risk score. Immunotherapy response-related analyses were then performed. Finally, cell-to-cell communication analysis was carried out for key cells identified based on prognostic gene expression analysis in annotated cells. Results: The six candidate migrasome-related genes were identified through the overlap of 5158 DEG set A, 1960 key module genes, and 146 DEG set B. Further screening led to the selection of T1MP1, CXCL8, and MGP as potential prognostic biomarkers. Immune-related analysis indicated that the high-risk group exhibited a better response to immunotherapy. Notably, the prognostic genes showed elevated expression levels in monocytes and tissue stem cells, thereby designating them as key cell types. Conclusions: We conducted bioinformatic analysis of migrasome-related genes and identified significant involvement of T1MP1, CXCL8, and MGP in influencing CRC prognosis and immunotherapy response. Our research provides novel insights into the role of migrasomes in CRC biology.