Two decades have gone by since the earlier trials of alpha-fetoprotein (AFP) screening for hepatocellular carcinoma (HCC) were conducted in Africa and China. It is accepted that early detection, diagnosis and treatment of HCC remains an important target to be achieved before a breakthrough appears on the primary prevention of HCC. In the present study, screening investigations were performed in a high risk population of HCC, defined as persons who had hepatitis, blood transfusions, a family history of HCC, and were hepatitis B virus carriers. Ultrasonography combined with AFP serosurvey was accepted as an effective screening procedure to detect small HCC. Early diagnosis of HCC was not difficult if tumour markers and medical imaging were combined. Early resection has been proven to prolong survival of patients with small HCC. Repeated intralesional ethanol injection is an alternative treatment to surgery, while transcatheter arterial embolization is a less effective alternative. Re-resection of subclinical recurrence after curative resection has proven of merit in prolonging survival even further. Resection of small HCC remains an important approach in getting long-term HCC survival and to improving 5-year survival rates. It is more effective than treatment of large HCC. Studies on the secondary prevention of HCC have stimulated research into tumour markers, the natural history and cellular origin of HCC and oncogenes. However, the issue of ‘cost-effectiveness’ remains to be evaluated.