Background: This study was performed to quantify the expression of Golgi protein-73 (GP73) in healthy controls and in patients with liver disease, and to evaluate the correlations between GP73 and other serum markers in different liver diseases. Methods: Serum GP73 was measured in 478 healthy controls and 296 patients with different types of liver disease. Quantitative hepatitis B virus (HBV) DNA was determined in two chronic hepatitis B (CHB) groups. Other serum liver fibrosis markers were measured in the liver fibrosis group and alpha-fetoprotein (AFP) was measured in hepatocellular carcinoma (HCC) group. The correlations between GP73 and these markers were evaluated. Results: The GP73 value in hepatitis B e antigen (HBeAg)positive CHB group, HBeAg-negative CHB group, liver fibrosis group and HCC group was significantly higher (p < 0.001) than that in healthy controls. GP73 showed significant correlation with other markers in the liver fibrosis group and with AFP in the HCC group. Conclusions: Compared with healthy controls, GP73 in patients with liver disease was significantly increased. With the progression of liver disease, GP73 showed a significantly increasing trend. These results suggest that GP73 might be used as a serum marker for the diagnosis of liver diseases and for monitoring disease progression.