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Background: Circulating tumor cells (CTCs) have been investigated as a potential biomarker for predicting prognosis and monitoring therapeutic responses in colorectal cancer (CRC). However, the sensitivity of CTCs detection is low, thus limiting the clinical utility of CTCs. We aim to examine the clinicopathological parameters that improve prognosis prediction for CRC using CTCs as a biomarker. Methods: We enumerated CTCs in 186 CRC patients and associated the number of CTCs with the clinicopathological features and overall survival (OS) using a univariate and multivariate Cox regression model and Kaplan-Meier survival analysis. Results: The presence of CTCs from 186 CRC patients was significantly associated with stage, preoperational carcinoembryonic antigen (CEA), and CA19-9 levels. Using Kaplan-Meier survival and Cox regression analysis, patients with five or more CTCs exhibited significantly worse OS compared to patients with fewer than five CTCs. The combination of CTCs with tumor marker CEA has a better OS prediction than individual CTCs or CEA and serves as a more effective prediction model in patients with CRC. Conclusion: We identified that patients with more than five CTCs exhibited significantly worse OS. Additionally, patients with the normal level of CEA, but who also had more than five CTCs trended towards a worse OS. [ABSTRACT FROM AUTHOR]