Abstract: Objective：To investigate the expression of metadherin (MTDH) in hepatocellular carcinoma (HCC) and its role in promoting HCC metastasis.Methods：The expression of MTDH in HCC and adjucent normal tissues was detected. Co-Immunoprecipitation (Co-IP) and mass spectrometry was used to investigate the protein complex involving MTDH. Results：The expression of MTDH was significantly higher in HCC tumors than that in corresponding normal liver tissues, and tumors with microvascular invasion, pathological satellites, poor differentiation, or TNM stage ⅡⅢ were prone to exhibit higher MTDH expression (P<0.01). The clinical outcome was poorer in the MTDH high group than that in the MTDH low group in both the 1, 3, 5year overall survival rates (OS) and the 1, 3, 5year cumulative recurrence rates (P<0.05). COIP results showed that MTDH can form a complex with PRMT5.Conclusions：MTDH can accurately predict the poor outcome of HCC patients after surgery, and is a great independent prognostic indicator.