[Abstract] Objective: To explore the relationship between cerebral endothelial cell adhesion molecule (CERCAM) and prognosis of colon cancer patients, so as to establish a nomogram with good prognostic value by using Cox model and verify its diagnostic value. Methods: The expression profile of CERCAM in colon cancer tissues and normal tissues as well as clinicopathologic data of colon cancer patients were downloaded from TCGA and GTEx databases. At the same time, colon cancer and paracancerous tissue samples collected from 4 colon cancer patients admitted to Nanjing First Hospital from Feburary 2013 to June 2019 were used for verification. Firstly, differential analysis, pathway enrichment analysis, and survival analysis were performed to investigate the tissue localization, functional and prognostic value of CERCAM expression. In addition, Cox regression analyses was conducted to screen the risk factors for the prognosis of colon cancer. A nomogram was established based on CERCAM and various risk factors, and was verified and evaluated by concordance indices, calibration curves, and time-dependent receiver operating characteristic (ROC) curves. In addition, the survival curves were plotted according to risk stratification. Results: The expression of CERCAM in colon cancer tissues was significantly lower than that in normal tissues (P<0.001). The overall survival (P=0.032) and survival status (P=0.002) of colon cancer patients with high CERCAM expression level was significantly inferior to those with low CERCAM expression level. CERCAM was correlated with the activation of proteoglycans in cancer and PI3K-Akt signaling pathway. Cox analysis showed that CERCAM expression level (HR=2.22, P=0.015), T stage (HR=5.65, P=0.015), M stage (HR=2.62, P=0.022) were independent risk factors for prognosis of colon cancer, while vascular infiltration (HR=2.30, P=0.089) was a risk factor as well. Based on the above factors, a nomogram was established. The concordance indices suggested good discrimination of the nomogram, and the training set was consistent with the test set. The calibration curves and ROC curves also indicated good predictive ability of the nomogram. Survival curves plotted according to risk stratification suggested that the high-risk group had lower survival rates (P<0.000 1). Conclusion: High level CERCAM expression is correlated with the poor prognosis of colon cancer patients, which is possibly associated with proteoglycans in cancer and PI3K-Akt signal pathway. The nomogram established based on CERCAM is superior to the traditional prediction model, which has certain clinical value in predicting survival prognosis of colon cancer patients. This practical model is helpful for the risk stratification and the optimization of treatment plan.