Purpose: Neoplastic development is a multistep process that involves the accumulation of genetic alterations in protooncogenes, DNA repair genes, and tumor suppressor genes. Molecular studies in carcinoma have shown the high frequency of loss of heterozygosity (LOH) in some specific chromosome regions, but LOH on the HCC chromosome has not been thoroughly investigated in Korea. LOH is considered to be phenotypes of genomic instability. We investigated the genetic instability and microsatellite alterations of chromosome 5, 8, 13 and 17 in hepatocellular carcinoma (HCC). Methods: Microsatellite alteration analysis was performed using polymerase chain reaction with 12 polymorphic microsatellite markers (BAT26, D5S123, D5S346, D8S254, D8S261, D8S262, D13S153, D13S159, D13S171, D17S250, D17S796, TP53) in 37 surgically resected HCCs and their respective non-tumorous counterparts. Pairs of tumorous part and normal tissue in the same patient were compared and then the size of microsatellite markers was measured. Results: MSI was detected in 3 samples and LOH was detected in 51 samples of 37 cases. Fractional allelic loss (FAL) was above 0.2 in 10 cases and was correlate with high grade of HCC. we could detect only 1 case of LOH in D8S254 marker, which was advanced cancer. Markers D5S123 and D5S346 showed 2 and 3 cases of LOH, respectively. Markers D8S262, D17S250 and D17S796 had LOH and were significantly correlated with tumor grade. Conclusion: According to the results, our data revealed that specific LOH, rather than MSI, may be involved in hepatocarcinogenesis. LOH may be a useful tool for following HCC patients because the high frequency of LOH correlates with poor prognosis of HCC.