Hepatocellular carcinoma (HCC) is a major type of liver cancer with high mortality, which is a prevalent common cancer in the world. Aberrant miRNAs contribute to the progression and development of HCC. Currently, our study demonstrated that miR-4317 was decreased in HCC patient samples tissues and HCC cell lines, which was related to poor clinical features, including tumor size, advanced TNM stage and vascular invasion. Furthermore, we confirmed that miR-4317 suppressed cell viability, proliferation, invasion and migration through loss- and gain-of-function experiment in vitro. In addition, miR-4317 inhibited tumor growth in vivo experiment. Luciferase reporter assays confirmed that ZNF436 was a direct target of miR-4317. Restoration of ZNF436 reversed the role of miR-4317 on HCC. ZNF436 expression was increased in HCC tissues and cell lines, which was negatively correlated with miR-4317 expression. ZNF436 overexpression obviously promoted the cell proliferation, viability, invasion and migration of HCC cells. ZNF436 mediated the regulatory function of miR-4317 on PI3K/AKT pathway. Overall, our data suggest that miR-4317 is a novel tumor suppressor to suppress HCC progression through PI3K/AKT pathway by targeting ZNF436, and may serve as a prognostic biomarker and therapeutic target for HCC.