Objective To investigate the significance of XAGE-1bmRNA expression in the blood specimens of patients with primary liver cancer, cirrhosis and benign liver diseases and in healthy individuals. Methods Venous blood specimens of patients with primary liver cancer (n= 125), cirrhosis (n= 23), benign liver diseases (n= 34) and healthy individuals (n = 41 ) were collected. XAGE-1b mRNA was detected by real-time fluorescence quantitative PCR. Results The expression levels of XAGE-1b mRNA in patients with primary liver cancer, cirrhosis, benign liver diseases and healthy in dividuals were 3.72 (0.93, 10.2) ×10-5, 0 (0, 0. 56) ×10-5, 0 (0, 0)×10-5, 0 (0, 0) ×10-5, respectively. The XAGE-1b mRNA expression in patients with primary liver cancer was obviously higher than the patients with cirrhosis, benign liver diseases and in healthy individuals. The expression levels for patients with cirrhosis was higher than patients with benign liver diseases and in healthy individuals. The expression levels for patients with benign liver diseases and healthy individuals were similar. With a optimal cut-off value of 8. 385 × 10-7 , the sensitivity, specificity, positive predictive value, and negative predictive value of XAGE-lb mRNA for diagnosing primary liver cancer were 80. 0%, 89.8%, 90.9% and 77.9% respectively. The positive rates for patients with primary liver cancer and cirrhosis were 80.0% and 30.4% respectively. Conclusion XAGE-lb mRNA can be used as a tumor marker for primary liver cancer. It contributes to the differentiation between primary liver cancer, cirrhosis and benign liver diseases.