Objective To detect the methylation levels of PR domain-containing protein 12 (PRDM12), forkhead box E1 (FOXE1), beta-1,3-glucuronyltransferase 2 (B3GAT2), vimentin (VIM) and secreted frizzled-related protein 2 (SFRP2) genes in colorectal cancer tissues, so as to evaluate their potentials as early screening markers for colorectal cancer. Methods The paraffin specimen samples were collected from 31 colorectal cancer patients receiving surgical resection in Changhai Hospital, Naval Medical University (Second Military Medical University). The methylation levels of PRDM12, FOXE1, B3GAT2, VIM, SFRP2-1 and SFRP2-2 gene promoters in cancer tissues and corresponding paracancerous normal tissues were detected using pyrosequencing method. Results The promoter methylation indexes of PRDM12, FOXE1, B3GAT2, VIM, SFRP2-1 and SFRP2-2 genes were significantly higher in the cancer tissues of the 31 patients than those in the paracancerous tissues (all P<0.01). The positive methylation rates of PRDM12, FOXE1, B3GAT2, VIM, SFRP2-1 and SFRP2-2 gene promoters were 87.1% (27/31), 90.3 (28/31), 80.6% (25/31), 77.4% (24/31), 74.2% (23/31) and 64.5% (20/31), respectively. In the 18 cases of early stage (TNM Ⅰ-Ⅱ) colorectal cancer, the positive methylation rates of PRDM12, FOXE1, B3GAT2, VIM, SFRP2-1 and SFRP2-2 gene promoters were 88.9% (16/18), 94.4% (17/18), 83.3% (15/18), 77.8% (14/18), 83.3% (15/18) and 61.1% (11/18), respectively. Conclusion PRDM12 and FOXE1 genes show abnormal methylation in colorectal cancer tissues, suggesting that they may serve as potential molecular markers for the early diagnosis of colorectal cancer.