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BACKGROUND miRNA-424-5p (miR-424-5p) has been implicated in the development and progression of various tumors. However, the functional mechanisms of miR-424-5p in hepatocellular carcinoma (HCC) are unclear. In this study, we investigated the specific biological functions of miRNA in HCC. METHODS The expression of miR-424-5p was measured by qRT-PCR in HCC tissues and cell lines. Western blot and immunohistochemistry were used to detect the protein expression level of TRIM29. The relationship between miR-424-5p and the clinicopathological features of HCC patients was analyzed. Cell function experiments were performed to examine proliferation and invasion in HCC cells. The miRNA database was used to predict downstream target genes of miR-424-5p, which were verified by a luciferase reporter assay. Furthermore, cell and animal experiments confirmed that miR-424-5p exerts its biological function through the target gene TRIM29. RESULTS miR-424-5p expression was decreased in HCC tissues and cell lines, and correlated with AFP, TNM stage, intrahepatic metastasis and poor overall survival in HCC. The upregulation of miR-424-5p inhibited cell proliferation and invasion in vitro and suppressed HCC tumor growth in vivo. TRIM29 was confirmed to be the downstream target gene of miR-424-5p. Finally, rescue experiments suggested that the upregulation of TRIM29 could rescue inhibitory effect of miR-424-5p overexpression on cell proliferation and migration. CONCLUSION miR-424-5p is a tumor suppressor miRNA that inhibits cell proliferation and invasion via directly modulating TRIM29, which is related to cell proliferation and invasion in HCC. Thus, miR-424-5p may be a potential therapeutic and new prognostic marker for HCC.