Abstract: Objective：To investigate the expression of protein arginine methyltransferase 5 (PRMT5) in hepatocellular carcinoma (HCC) and its clinical significance. Methods：PRMT5 expression in tumor tissues of 323 HCC patients as well as corresponding normal liver tissues was examined by immunohistochemical staining, the expression of PRMT5 in tumor tissues and its distribution in cells were analyzed. The relationship between the expression and distribution of PRMT5 and the clinical features and prognosis of HCC patients were analyzed, meanwhile, the prognostic value of PRMT5 combined with metadherin （MTDH） for HCC patients was also investigated. Results：Immunohistochemical results showed that PRMT5 expression level in most of the tumor tissues were significantly higher than that in the corresponding non-tumorous tissues, and the distribution of PRMT5 varied among patients,with PRMT5nuclear accounting for 36.8% (119/323) of all the patients. The expression and distribution of PRMT5 were correlated with MTDH expression (P<0.01). The expression of PRMT5 had no prognostic value for HCC patients. However, the survival rate and recurrence rate were better in the PRMT5nuclear group than those in the PRMT5cytoplasm group (P<0.05). PRMT5 intracellular distribution combined with MTDH expression yielded better accuracy than used alone (P<0.001). Conclusions：The predominance of PRMT5 in extranuclear distribution of HCC cells suggests poor prognosis. PRMT5 intracellular distribution combined with MTDH is better prognostic parameters than used alone.