Objective:To investigate the expression and significance of HepPar1,armor embryo protein(AFP),CD34,CD10 and CEA in hepatocellular carcinoma(HCC) with negative serum AFP. Methods:The expression of HepPar1,AFP,CD34,CD10 and CEA was tested by immunohistochemistry in 100 HCC samples with negative serum AFP. Results:In HCC with negative serum AFP,the expression rate of HepPar1 was 86%,and had close correlation with the differentiation,structure type,cytological subtypes and the number of lymphocyte around the tumor;the expression rates of AFP and CD34 were 18% and 87% respectively,and had both close correlation with the number of caryocinesis and cytological subtypes;the expression rate of CD10 was 41%,and had close correlation with the cytological subtypes and gender;the expression rate of CEA was 71%,but had no correlation with the clinical features. Conclusion:Unique immunohistochemical characteristics exist in HCC with negative serum AFP.