ABSTRACT. We evaluated the clinical significance and explored the prognostic value of serum endothelial cell-specific molecule-1 (ESM-1) expression in colorectal cancer (CRC) in a Chinese population. Serum samples were obtained from 89 CRC patients undergoing surgical treatment and 90 healthy volunteers (control group). ESM-1 levels in serum samples from CRC patients and controls were measured using a sandwich enzyme-linked immunosorbent assay. Overall survival was analyzed by the log-rank test, and survival curves were plotted according to the Kaplan-Meier method. Univariate Cox regression was performed on each clinical covariate to examine its influence on patient survival. Final multivariate models were based on step-wise addition. Serum ESM-1 expression levels were significantly higher in patients with CRC (66.81 ± 22.97 pg/mL) than in healthy volunteers (31.50 ± 16.81 pg/mL, P = 0.012). Expression levels of ESM-1 in CRC patients were significantly correlated with histological differentiation (P = 0.004), TNM stage (P = 0.007), depth of tumor invasion (P = 0.02), and lymph node metastasis (P = 0.001). Kaplan-Meier survival curves revealed that the overall survival was significantly lower in patients with high ESM-1 levels than in those with low levels (29.43 vs 61.20%, P = 0.0166). Multivariate analysis confirmed that the hazard risk of 5520 H. Jiang et al. ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (2): 5519-5526 (2015) death was significantly higher in patients with high serum ESM-1 expression compared with low expression (hazard risk = 4.09, 95% confidence interval: 2.27-10.88, P < 0.001). Detection of ESM-1 levels in the serum may serve as a tumor biomarker for assessing prognosis in CRC.