Tumor mutation burden (TMB) level is identified as a useful predictor in multiple tumors including colon adenocarcinoma (COAD). However, the function of TMB related genes has not been explored previously. In this study, we obtained patients’ expression and clinical data from The Cancer Genome Atlas (TCGA) and the National Center for Biotechnology Information (NCBI). TMB genes were screened and subjected to differential expression analysis. Univariate Cox and LASSO analyses were utilized to construct the prognostic signature. The efficiency of the signature was tested by using a receiver operating characteristic (ROC) curve. A nomogram was further plotted to assess the overall survival (OS) time of patients with COAD. In addition, we compared the predictive performance of our signature with other four published signatures. Functional analyses indicated that patients in the low-risk group have obviously different enrichment of tumor related pathways and tumor infiltrating immune cells from that of high-risk patients. Our findings suggested that the ten genes’ prognostic signature could exert undeniable prognostic functions in patients with COAD, which might provide significant clues for the development of personalized management of these patients.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12920-023-01555-2.