AIM: To evaluate whether DCP is better than AFP for differentiating HCC from nonmalignant liver disease and further evaluate the usefulness of DCP in early diagnosis of small HCC.METHODS: Serum DCP and AFP levels were determined in 127 patients. Among these patients, 32 were with noncirrhotic chronic hepatitis, 34 were with compensated cirrhosis, and 61 were with HCC. The cut-off value for the DCP and AFP were set as 40 mAU/mL and 20 ng/mL,respectively. To compare the diagnostic value of DCP and AFP in distinguishing HCC from nonmalignant chronic liver disease, receiver operating characteristic (ROC) curves were constructed for each assay.RESULTS: The accuracy, sensitivity, and specificity of DCP were higher than AFP in detecting HCC (81.9%, 77%,and 86.4% vs 68.5%, 59%, and 77.3%, respectively).The area under the ROC (AUROC) curves revealed that DCP had a better accuracy than AFP in diagnosis of HCC (0.85 [95%CT, 0.78-0.91] vs 0.73 [95%CI, 0.65-0.81],P = 0.013). In 39 patients with solitary HCC, the positive rates of DCP were 100% in patients with tumor size larger than 3 cm, 66.7% in patients with tumor size 2-3 cm and50% in patients with tumor size less than 2 cm. The positive rates of AFP in patients with tumor size larger than 3 cm, 2-3 cm and less than 2 cm were 55.6%, 50%,and 33.3%, respectively. The median level of DCP in HCC patients with tumor size larger than 3 cm was significantly higher than those with tumor size 2-3 cm and those with the size of less than 2 cm.CONCLUSION: Our study indicates that DCP has a better diagnostic value than AFP in differentiating HCC from nonmalignant chronic liver disease. DCP has not only a stronger correlation with HCC than AFP in tumor size but also more effectiveness than AFP in detecting small size of HCC.