Objective: To determine whether screening can lead to early detection of hepatocellular carcinoma (HCC) and improvement of long-term outcome. Methods: Alpha-fetoprotein (AFP) serosurvey plus ultrasonography have been employed as the principal screening approach for early detection of subclinical HCC. Results: During January 1971-December 1997, 2742 patients with pathologically proven HCC were retrospectively reviewed. Comparison between screening patients(n=1019) and clinical patients(n=1723), revealed the former to have a higher proportion of subclinical stage(74.1% vs 5.3%), a smaller tumor size (<;5cm, 52.1% vs 17.8%), a higher proportion of single tumors (71.6% vs 55.4%), a higher proportion of encapsulated tumors(65.5% vs 43.1%), a lower proportion of tumor emboli in the portal vein (6.8% vs 10.8%), a lower r-GTP level (<6 units, 44.5% vs 28.3%), a lower preoperative AFP level(<400ng/ml, 30.0% vs 25.0%), a higher resection rate (81.1% vs 58.0%), a higher radical resection rate(72.4% vs 66.6%), a lower operative mortality rate (2.5% vs 4.8%), a higher postoperative normalization of AFP level (37.5% vs 24.0%) and higher survival rates (5-year, 49.9% vs 32.5%; 10-year, 34.4% vs 24.0%). Conclusions: The significance of the role of screening for HCC is clear. It provides a hopeful chance of cure of HCC, has proven to be an important approach to improve overall prognosis, and has also led to changing concepts in clinical research into HCC.