Background To explore the clinical value of a combined detection of serum concentration of carcinoembryonic antigen (CEA), carbohydrate antigen 24-2 (CA24-2), and carbohydrate antigen 19-9 (CA19-9) for colorectal cancer (CRC).Methods The levels of serum tumor markers (CEA, CA24-2 and CA19-9) and clinicopathologic features in patients with colorectal cancer in Meizhou People's Hospital were evaluated. In addition, KRAS/NRAS, PIK3CA and BRAF mutations were detected in some patients with colorectal cancer.Results A total of 2,281 patients (1,420 males and 861 females) were recruited in the study, included 1,578 colorectal cancer patients and 703 controls. The levels of CEA, CA24-2 and CA19-9 in colorectal cancer group was significantly higher than control group. The sensitivities of three individual markers were lower than 30%, which individual sensitivity of the tumor markers sorted in descending order were CEA> CA19-9> CA24-2. The specificities of three individual markers were more than 92%, and the specificity sorted in descending order were CA24-2> CA19-9> CEA. The prediction equation excluding the risk of colorectal cancer was. Probability (normal) = Exp (-5.47 -0.28CEA -0.11 CA242 + 0.001 CA199)/ (1+ Exp (-5.47 -0.28CEA -0.11 CA242 + 0.001 CA199)). There were no significant differences in age, gender, histology type, differentiation, depth of invasion and TNM stage between mutations in KRAS/NRAS , BRAF and PIK3CA genes or not, respectively.Conclusions Serum CEA, ca24-2, and ca19-9 are valuable noninvasive indicators for the detection and screening of patients with early colon cancer. We need to look for other, more sensitive tumor markers.