Objective To develop an immune-related genes (IRGs) based prognostic signature and evaluate the value in predicting prognosis in patients with colon cancer.Methods Gene chip data sets of 452 colon cancer patients were collected from the TCGA database, and 2 498 IRGs data sets were obtained from the ImmPort database. After taking the intersection, univariate Cox proportional risk regression analysis and multivariate Cox proportional risk regression analysis were used to screen and construct the IRGs gene model. To evaluate the prognostic value of genetic models, Kaplan-Meier survival analysis was used to analyze the relationship between IRGs model and prognosis of patients with colon cancer, and Cox proportional risk regression was used to analyze the correlation between IRGs model and clinicopathological features of colon cancer. The relationship between risk score and immune cell infiltration was analyzed.Results A total of 206 differentially expressed IRGs were identified in colon cancer tissues, and 11 IRGs were identified by univariate proportional risk regression analysis and multivariate Cox proportional risk regression analysis. These were solute carrier family 10 member 2 (SLC10A2), C-X-C motif chemokine ligand 5 (CXCL5), C-C motif chemokine ligand 28 (CCL28), immunoglobulin kappa variable 1D-42 (IGKV1D-42), chromogranin A (CHGA), endothelial cell specific molecule 1 (ESM1), gastrin releasing peptide (GRP), stanniocalcin 2 (STC2), urocortin (UCN), oxytocin receptor (OXTR) and immunoglobulin heavy constant gamma 1 (IGHG1). Colon cancer patients were divided into high risk group and low risk group according to the median value of risk value of IRGs risk markers. Patients in the high risk group had shorter overall survival (OS) than that in the low risk group (P< 0.001). The area of the time-dependent ROC curve (AUC) was 0.754, suggesting that IRGs model had a good ability to predict the prognosis of colon cancer patients. The higher the risk value of IRGs, the later T stage of colon cancer (T3-T4), the more lymph node metastasis (N1-N2) and the later clinical stage of colon cancer (Ⅲ-Ⅳ), P<0.05. Except for neutrophils, the infiltration density of B cells, CD4+ T cells, CD8+ T cells, dendritic cells and macrophages in high-risk group was significantly increased (P<0.05).Conclusion The risk values of the 11 IRGs gene models screened in this study can be used to predict the prognosis of colon cancer patients, and can be used as biomarkers to evaluate the prognosis of colon cancer patients.