P21WAF1/Cip1, an inhibitor of cyclin-dependent kinases, is a critical downstream effector in the P53-specific pathway of growth control. Increased expression of P21WAF1/Cip1 has been found to reflect the status of the P53 tumor-suppressor pathway. We investigated the expression of P21WAF1/Cip1 in a relatively small, but well-characterized group consisting of 28 hepatocellular carcinomas. The samples were previously studied for P53 gene mutation. P21WAF1/Cip1 expression were identified by in situ hybridization and immunohistochemistry. Positive ISH for P21WAF1/Cip1 transcripts was found in 18 of 28 cases (64.3%). All positive cases by ISH showed detectable P21WAF1/Cip1 protein reactivity by IHC. No relationship was found between P21WAF1/Cip1 staining and P53 mutational status. No associations were seen with tumor metastasis, size and tumor grade, except for tumor differentiation status which showed higher frequency of P21WAF1/Cip1 expression in moderate-well differentiated HCCs than poorly differentiated tumors (P < 0.05). It is concluded that expression of P21WAF1/Cip1 is common in HCCs, but does not correlate with P53 mutational status or pathological parameters investigated except for tumor differentiation. Also, there may be other factors beside P53 that regulate P21WAF1/Cip1 gene expression in HCCs.