Background: This study aimed to evaluate the diagnostic value of α-1-acid glycoprotein (AGP) to improve the diagnosis of hepatocellular carcinoma (HCC). Methods: AGP was measured in serum of 53 HCC patients and 20 liver cirrhosis (LC) patients, in addition to 15 healthy individuals. The diagnostic performances of AGP was determined and compared with alpha fetoprotein (AFP) for the diagnosis of HCC using area under the ROC curve (AUC). Results: In the patients with HCC, the mean serum concentration of AGP was 1.38 ± 0.4 ng ml-1. As expected, it was significantly higher than that of the LC group (1.12 ± 0.4 ng ml-1, P< 0.05). The detection of HCC using AGP produced better AUC (0.74), sensitivity (74%) and specificity (75%) compared to AFP at cutoff 400 (U L-1) had AUC (0.70), sensitivity (40%) and specificity (95%). The combination of AFP and AGP had AUC (0.84), sensitivity 74%, specificity 80 %