Undetected micrometastasis may play a key role in the early relapse of colorectal cancer (CRC) patients. The aim of this study was to detect circulating tumor cells (CTCs) for predicting early relapse of CRC patients by a weighted enzymatic chip array (WEnCA) and analyze 15 candidate genes associated with CRC carcinogenesis. The genes of 105 postoperative CRC patients were analyzed by membrane array and direct sequencing. We constructed a WEnCA platform including five prognosis-related genes and analyzed the detection rate of WEnCA for CTCs in 30 clinically confirmed CRC relapse patients. Postoperative relapse was significantly correlated with gene overexpression, including EVI2B (p=0.001, OR=4.622), ATP2A2 (p=0.006, OR=4.688), S100B (p=0.001, OR=11.521), TM4SF3 (p=0.001, OR=6.756), and OLFM4 (p=0.008, OR=3.545). Using WEnCA (weighting score of each gene: 5 to EVI2B, 5 to ATP2A2, 12 to S100B, 7 to TM4SF3, and 4 to OLFM4), we could detect CTCs presenting these genotypes in relapsed CRC patients. The sensitivity, specificity, and accuracy were 94.7%, 93.5%, and 97%, respectively. The results of the present study suggest that EVI2B, ATP2A2, S100B, TM4SF3, and OLFM4 could be potential prognostic markers for CRC patients.