With respect to hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), primary, secondary, and tertiary prevention measures have been or should be adopted. In primary prevention, behavioral patterns represent an important risk factor for HBV infection and should be controlled, discouraging those favoring infection. Interferon treatment shows a modest effect in reducing HCC risk in treated patients, but the data obtained cannot be converted in clinical practice. Nucleoside analogs significantly reduce, but do not abolish, HCC risk in patients with cirrhosis, and should therefore be used in patients with cirrhosis and also to diminish the risk of the other potential complications. With respect to secondary prevention, surveillance with semiannual ultrasound examination is indicated in patients with HBV-related cirrhosis as well as in other subgroups of patients, depending on racial and geographical pattern. Finally, the role of interferon in tertiary prevention of HCC relapse after radical treatment is still under debate; some evidence in favor of the treatment is present, but side effects due to toxicity are frequent and severe enough to limit patients' compliance substantially. As there is definitely no agreement on the efficacy and cost-effectiveness of antiviral treatment in HCC prevention, there is still a need for well-constructed, large size, and randomized prospective trials to confirm what is still required based on expert opinion rather than on sound scientific evidence.