Objective To detect the expression of apurinic/apyrimidinic endonuclease 1 (APEI) and explore its correlation with the expression of mutant p53 in hepatocellular carcinoma (HCC). Methods The expression of APE1 and mutant p53 was detected by SP immunohistochemical method in 10 specimens of normal liver tissue, 40 specimens of liver cirrhosis tissue and 103 specimens of HCC tissue which were collected at the Department of Pathology of Daping Hospital from 1991 to 2004. All data were analyzed by chi-square test, correla-tion analysis and K Independent-Samples Tests. Results The expression rate of APE1 in HCC was 100.0%, which was significantly higher than that in normal liver tissue (40.0%) and liver cirrhosis tissue (82.5%) (χ~2= 47.852, P < 0.01). The expression of APE1 was only detected in the nucleus in normal liver tissue. Ectopic expression of APE1 in cytoplasm was detected in liver cirrhosis tissue and HCC tissue, with the rate of 20.0% and 53.4%, respectively (χ~2=20.757, P <0.01). There was statistical difference in clinical staging and pathological grading of HCC with different combinations of APE1 expression (intranuclear or ectopic expression) and mutant p53 expression (positive or negative expression) (χ~2=12.910, 14.481, P < 0.01), and HCC with ectopic expression of APE1 and positive expression of p53 had high malignant degree. Conclusion Overexpression and ectopic expression of APE1 in cytoplasm may play important roles in the genesis and progression of HCC, and the ectopic expression of APE1 and p53 mutation may have synergistic effect.