Objective:To investigate the clinical significance of IMP3 expression, and to detect the relationship between IMP3 expression and genetic methylation. Methods:Paraffin sections of tumor tissues from 162 patients with HCC were examined for IMP3 expression by immunohistochemistry. Correlation analysis of clinical factors and IMP3 expression level was performed. One hundred and sixty-two patients with post-operation of HCC were follow-up for long-term survival analysis. P1 and P2 of IMP3 gene from normal and tumor tissues were detected by methylation-specific PCR and DNA sequencing. IMP3 protein was detected by Western Blot from cultured normal liver cells L02 and Huh7 hepatoma cells. DNA was extracted from two groups of cells,and the methylation status of promoter region CpG islands in IMP3 gene was detected. Results:IMP3 was expressed in 67.90% of HCC. IMP3 expression is related to age,tumor size, grading, staging,AFP,early relapse,but not gender and HBsAg. One hundred and sixty-two cases of postoperative follow-up found that postoperative long-term survival rate of IMP3 negative group was significantly higher than that of the IMP3-positive group(P < 0.01). Detection of P1 and P2 by methylation-specific PCR showed that CpG islands from P1 and P2 of tumor tissues showed unmethylated modification,however,those of normal tissues showed methylated modification. Normal liver cells were IMP3 negative,Huh-7 hepatoma cells showed strongly positive IMP3 expression. P1 and P2 of normal liver cells were highly methylated,and P1 and P2 of Huh-7 hepatoma cells showed unmethylated status. Conclusion:The level of IMP3 expression is high in HCC,and high IMP3 expression suggests poor prognosis;DNA methylated modification may participate in the processes,which regulates and controls IMP3 expression.