Abstract: Objective : To determine the value of hepatoma-specific alpha-fetoprotein (HS-AFP) in the early diagnosis and differential diagnosis of hepatocellular carcinoma (HCC). Methods : HS-AFP and AFP were measured in 105 cases with HCC and 151 cases with benign liver diseases. There were 10 cases of benign liver diseases with positive HS-AFP that were followed up for 15 months. Total protein was separated with polyacrylamide gel electrophoresis (PAGE) in a discontinuous buffer system and HS-AFP was detected by Western blot. AFP was detected by chemiluminescence. Results : In the 105 cases of HCC, the positive rates of HS-AFP and AFP>200 μg/L were 60.0% and 50.5%, respectively (P>0.05). In the cases of benign liver diseases, the positive rate of HS-AFP was significantly lower (P<0.05). In the cases with AFP of 50μg/L to 400μg/L, the positive rate of HS-AFP was 77.1% in HCC and 13.6% in benign liver diseases. Of the 10 cases of benign liver diseases with positive HS-AFP, 3 of them developed HCC during the follow-up period. In the 11 cases with small HCC, the positive rate of HS-AFP (45.5%) was significantly higher than that of AFP (18.2%). Conclusion : HS-AFP was a better marker than AFP in the diagnosis of HCC. Monitoring HS-AFP in a high risk population was useful for early diagnosis of HCC. HS-AFP plays an important role in the differential diagnosis between HCC and benign liver diseases in patients with slight to moderate elevation of serum AFP.