BACKGROUND/AIMS: p53 mutation is the most common genetic abnormality in human cancers. However, although it has been reported that p53 overexpression in hepatocellular carcinoma (HCC) is associated with the aggressive behavior of tumor, the prognostic significance of p53 overexpression in HCC remains controversial. The aims of the present study were to examine the correlations between p53 overexpression and the clinicopathologic parameters of HCCs, and to determine the prognostic significance of p53 overexpression in HCC. METHODS: Immunohistochemical analysis of p53 overexpression was performed in 105 consecutive cases of HCC who underwent curative hepatic resection. Survival curves were calculated using the Kaplan-Meier method and multivariate analysis of outcome predictors for HCCs was assessed by logistic regression analysis. RESULTS: p53 overexpression was observed in 20 of 105 HCCs (19.0%). Multivariate analysis identified significant correlations between p53 overexpression and microvascular invasion (p=0.027), liver cirrhosis (p=0.035), 1-year survival rate (p=0.016), multiple tumors (p=0.014), and the presence of tumor capsule (p=0.010). The 2-year survival rate was poorer in patients without tumor capsule (p=0.043). CONCLUSIONS: Our results show a positive association between p53 overexpression and microvascular invasion in HCC, and indicate that p53 overexpression is a poor prognostic factor of survival, especially within 1 year after liver resection in HCC patients.