Objective:To investigate the level of nucleolin in serum of colorectal cancer patients and its clinical significance. Methods:The levels of serum nucleolin in 172 patients with colon cancer,24 patients with rectal cancer and 80 healthy controls were determined by enzyme linked immunosorbent assay (ELISA). The relationship between serum nucleolin level in colon cancer and clinical features and pathological features were analyzed. Results:The serum nucleolin level in colon cancer patients,rectal cancer patients,and healthy controls were 228.9 ± 212.4 pg/mL,115.1 ± 34.5 pg/mL and 101.1 ± 32.4 pg/mL. The serum nucleolin level in colon cancer patients was significantly higher than that in healthy controls (P < 0.001),and there was no significantly difference between rectal cancer patients and healthy controls (P > 0.05). The sensitivity and specificity of serum nucleolin detecting in colon cancer were 91.9% and 83.8%,and serum carcino-embryonic antigen (CEA)were 68.6%,85.0%,respectively. The level of nucleolin in serum of infiltrating type colorectal cancer was significantly higher than that in protruded type and ulcerative type (P < 0.05). There was no correlation with the serum nucleolin level in colon cancer and age,gender,tumor size,differentiation degree,degree of invasion,lymph node metastasis,distant metastasis,TNM stage,and Ducks stage. Conclusion:The detection of serum nucleolin level in colon cancer patients has a high sensitivity and specificity,and the sensitivity is better than CEA and the specificity is as similer as CEA. Serum nucleolin may be potential valuable for colon cancer diagnosis.