Hepatocellular carcinoma (HCC), especially hepatitis B virus (HBV)-related, remains a major cause of cancer-related mortality worldwide. Unless there is early detection with curative treatment, the 5-year survival rate of advanced HCC is less than 15％. The preventive strategies for HBV-related HCC are thus urgently needed to reduce the global burden of this disastrous cancer. Primary prevention involves the avoidance of viral infection through hepatitis B vaccination and interruption of viral transmission from patients with chronic HBV infection. Universal neonatal hepatitis B vaccination program has successfully reduced the prevalence of HBV carriage rate as well as HCC incidence in vaccinated cohorts. However, HBV elimination is still difficult to achieve. Regarding secondary prevention, long-term treatment with nucleos(t)ide analogues has been proven to reduce the risk of HBV-related HCC. Individual risk stratification and a periodic HCC surveillance in these patients could facilitate early HCC diagnosis. Finally, tertiary prevention can also be achieved by life-long treatment with NAs to reduce the risk of HCC recurrence after curative treatment of primary HCC. Challenges ahead include the fact that HBV is not yet curable by current antiviral agents. Combination therapy with direct anti-HBV agents and host-targeting immunomodulatory agents is under active development. In addition, HCC risk cannot be eliminated even in patients with HBsAg seroclearance or functional cure. Therefore, HCC surveillance is strongly recommended for every patient with chronic HBV infection.