The nuclear matrix is the non-chromatin skeleton of the nucleus. This structure contributes to the shape of the nucleus and regulates various nuclear functions. In this study, nuclear matrix proteins of human normal liver, a liver cancer cell line, HepG2, and hepatocellular carcinomas (HCC) were investigated. Using high resolution two-dimensional polyacrylamide gel electrophoresis, the nuclear matrix proteins of 3 normal liver and 14 HCC were compared and contrasted. A high degree of similarity between normal liver, HepG2, and HCC nuclear matrix protein patterns was found. Two HCC specific nuclear matrix proteins were identified. Among these, one protein (HCC-1, Mr 62 kd, pI 5.3) appeared in all tumor samples and HCC-2 (Mr 33.25, pI 5.3-5.5) was present in 9/11 tumors, but absent in normal liver and HepG2. Our results indicate the presence of HCC specific nuclear matrix proteins. These matrix proteins may be used as markers for HCC.