Enhancer RNAs (eRNAs) are a subclass of long noncoding RNAs (lncRNAs) that have a wide effect in human tumors. However, the systematic analysis of potential functions of eRNAs-related genes (eRGs) in colon cancer (CC) remains unexplored. In this study, a total of 8231 eRGs including 6236 protein-coding genes and 1995 lncRNAs were identified in CC based on the multiple resources. These eRGs showed higher expression level and stability compared to other genes. What's more, the functions of these eRGs were closely related to cancer. Then a prognostic prediction model with 12 eRGs signatures were obtained for colon adenocarcinoma (COAD) patients. ROC curves showed the AUCs were 0.81, 0.77, and 0.78 for 1-, 3-, and 5-year survival prediction, respectively. And the prognostic model also manifested good performance in the validation datasets. Besides, the expression levels of two prognostic signatures, TMEM220 and LRRN2, were verified to be significantly lower in CC tissues than in adjacent noncancerous tissues (p < .05). Finally, the distinct molecular features were characterized between the high- and low-risk group through multiomics analysis including DNA mutation and methylation. Our results show eRGs signatures based prognostic model has high accuracy and may provide innovative biomarkers in COAD.