Objective　To explore the expression and significance of p21WAF1 and p53 in HCC. Methods　Immunohistochemical method (IHC) was used to localize and semi-quantitate the proteins of p21WAF1 and p53 and to observe the relationship between the expression of p21WAF1 and the different histopathologic characters in 38 patients of HCC and their peri-cancer tissue as well as 5 normal liver tissue. Results　Of all 38 cases, both p21WAF1 and p53 expression were significantly higher in tumor than that in corresponding non-tumors liver tissue; 14 (36.8 %) of 38 cases showed p21WAF1 positive staining, 28 cases (73.7 %) were p53 positive, p21WAF1＋/p53＋ or p21WAF1-/p53－ were observed in 18, while 20 cases showed p53＋/p21WAF1－ or p53－/p21WAF1＋. p21WAF1＋ was seen in 1 of 38 (2.6 %) corresponding non-cancerous tissue and 2 of 5 normal liver tissue. p53 protein was not detected neither in the non-tumorous tissue nor in normal liver. No significant association was found between the expressions of p21WAF1 and p53(P＞0.05) in HCC. Their was no significant correlation between p21WAF1 or p53 expression and the different histopathologic characters of tumor (differentiating grades, intrahepatic metastasis and/or cancerous thrombi within portal veins). Conclusion　Both p21WAF1 and p53 proteins are over expressed in HCC than that in corresponding non-tumorous liver tissue, but there is no relationship between them. Both p53-independent and p53-dependent mechanism may play a role in regulating p21WAF1 expression in HCC. p21WAF1 immunostaining cannot be used to assess the status of p53 in any given cell or tissue.