The rate of HBV DNA integration into the genome of hepatocellular carcinoma (HCC) cells varies greatly among HCC tissues from different geographical districts. Because of the potential etiological significance of identifying HBV DNA integration in HCC tissues from Korea, we investigated 13 aseptically obtained HCC surgical specimens by Southern blot analysis. Among 13 HCCs, eight (61.5%) contained integrated HBV DNA. Of eight HBsAg-positive patients, six (75%) had integrated HBV DNA in their HCCs while two (40%) out of five HBsAg-negative patients had integrated HBV DNA. Those two HBsAg-negative patients with integrated HBV DNA were all anti-HBs-positive. However, it was not demonstrated in the patient without any HBV serological markers. These findings highly suggest a prominent etiologic role of HBV in the development of HCC. On the other hand, it also strongly favors a multifactorial etiology of human HCC in korea.