Objective To investigate the expression of HERV-HLTR-associating protein 2(HHLA2).in hepatocellular carcinoma(HCC) tissue and its relationship with different pathological grades,clinical stages,liver function and serum AFP level.Methods The positive rate of HHLA2 expression in 150 cases of paraffin-embedded HCC tissues was detected by immunohistochemistry.Ten cases of normal liver tissue specimens from health donors served as the normal control.The differences of HHLA2 expression in HCC tissues were compared among different pathological grades,clinical stage,liver function grades and serum AFP levels.Results The positive expression rate of HHLA2 in HCC tissue was significantly higher than that in normal control (P＜0.05).The positive rate of HHLA2 expression in low differentiated HCC tissue was highest.The positive rate of HHLA2 expression in the low differentiation and moderate differentiation HCC groups was significantly higher than that in the high differentiation group (P＜0.05).The positive expression rate in the patients with Barcelona stage C and D was significantly higher than that in the patients with the stage A and B(P＜0.05).The positive expression rate in the patients with Child-Pugh stage A was significantly higher than that in the patients with stage B and C(P＜0.01).While the HHLA2 expression rate had no statistically significant difference among different ages and different serum AFP levels(P＞0.05).Conclusion The positive expression rate of HHLA2 in cancer tissues of HCC patients is significantly increased.HHLA2 might play a certain role in the occurrence,development and metastasis of HCC.