Abstract: To investigate the expression of Raf kinase inhibitor protein (RKIP) and P-RKIP in hepatocellular carcinoma (HCC) and their relation with the invasion and metastasis of HCC. Methods Immunohistochemistry and western-blot was used to detect the expression of RKIP and P-RKIP in HCCs, paratumor tissues and normal liver tissues. Statistical analysis was used to determine the relationship between their expression and clinicopathological parameters. Results Statistical analysis revealed that the expression level of RKIP and P-RKIP in tumor tissue were significantly lower than that in tumor-surrounding tissue and in normal liver tissue（P<0.05）. RKIP and P-RKIP expression are dramatically lower in HCC with intrahepatic or lymphatic metastasis than that in without respectively. In moderately and well differentiated HCC both RKIP and P-RKIP positive stain rate is significantly higher than that in poorly differentiated HCC. There was a positive correlation between RKIP and P-RKIP expression in HCCs（P=0.000） and in paratumor tissues（P=0.005）. Conclusion Our findings indicate that down-regulation of RKIP and P-RKIP expression may serve as a risk marker for HCC development, progression and metastasis.