This paper provides a review of the known genetic diagnostic indicators of liver cancer. The correlation between the genetic diagnosis and clinical outcome in patients with hepatocellular carcinoma (HCC) has been widely reported, based on the detection of liver-specific mRNA or tumor DNA in the blood. Our results suggest that an alteration of alpha-fetoprotein (AFP) mRNA in peripheral blood from HCC patients during the perioperative period might permit the prediction of early recurrence after surgery. The presence of circulating HCC cells may be indicative of metastasis if liver-specific AFP mRNA is detected in the peripheral blood. However, some studies showed that sensitive RT-PCR might possibly give rise to false positivity because nontumor hepatocytes would also express low levels of AFP mRNA. Recently, quantification of AFP mRNA for HCC cell detection using real-time PCR or semiquantitative RT-PCR has proven useful in the prediction of metastasis/recurrence. On the other hand, circulating liver tumor DNA such as p16 and p15 methylation and mitochondrial mutations in the plasma and serum of liver cancer patients might be useful for monitoring, similar to the tumor markers. In future, HCC-specific genes and genes sensitive to radiation and chemotherapy are expected to have wide-spread clinical applications.