Background and study aim: The outcome of patients with hepatocellular carcinoma (HCC) remains poor because of late diagnosis. We aimed to evaluate the performances of serum alpha -1-acid glycoprotein (AAG) for the diagnosis of HCC, especially for HCC with low alpha-fetoprotein (AFP). Patients and Methods: Ninety patients included in this study, Session [CurrentTestPartID] had HCC, and 30 (50%) of these were AFP low HCC (AFP ≤20 ng/mL). The remaining 30 patients were chronic hepatitis C and cirrhosis without HCC as control group. Plasma AAG was analyzed using quantitative enzyme immunoassay technique. Results: Serum level of AAG was significantly elevated in low AFP HCC group compared with high AFP HCC and cirrhotic without HCC group, 1307.20 ± 9627 vs (850.82 ± 795.14 and 309.77± 220.17 respectively). Receiver operating characteristic (ROC) curve showed that the best cut off for AAG and AFP was 740 μg/ml and 20 ng/mL respectively. The area under the curve of AAG was significantly higher than that for AFP (0.95 vs 0.92) respectively. AAG at a cut-off value of 740 μg/ml provides higher sensitivity (73.3% vs 62%, respectively) and specificity (74.0%, and 71%, respectively) in low AFP HCC than high AFP HCC Conclusion: The role of AFP in the diagnosis of HCC is limited; AAG had better performance in diagnosing HCC patients with low AFP. So Serum level of AAG might be used as a potential diagnostic marker for hepatocellular carcinoma.