By regression analysis, 6 immune-related DEGs (AEN, F2RL1, NR3C2, PPARGC1A, LGALS4, and XDH) were identified as potential prognostic factors, of which AEN, LGALS4, and XDH were used to construct a risk score model, which can effectively predict overall survival (OS) in colon cancer patients. This evidence concerns the gene F2RL1 and colonic neoplasm.