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Background: To study the effect of microRNA‐383 (miR‐383) on cell proliferation, migration, and invasion of hepatocellular carcinoma (HCC) cells, and explore its mechanism. Methods: The expressions of miR‐383 and plant homology domain that refers to protein 8 (PHF8) were detected in tissues and cells by quantitative real‐time polymerase chain reaction (qRT‐PCR) or western blot respectively. The miR‐383 group (transfected miR‐383 mimics), miR‐con group (transfected miR‐con), si‐con group (transfected si‐con), si‐PHF8 group (transfected si‐PHF8), miR‐383 + ctrl group (cotransfected miR‐383 mimics and pcDNA‐3.1), miR‐383 + PHF8 group (cotransfected miR‐383 mimics and pcDNA‐3.1‐PHF8) were transfected into HepG2 cells by liposome method. Cell proliferation, migration and invasion were measured by 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) or trans‐well assays respectively. The luciferase activity of each group was detected by dual luciferase reporter gene assay. Results: Compared with normal adjacent tissues, the expression of miR‐383 was significantly down‐regulated and the expression of PHF8 was significantly up‐regulated (p <.05). Compared with normal hepatocellular cell LO2, the expression of miR‐383 was significantly reduced (p <.05) in HCC cells. Moreover, overexpression of miR‐383 or silencing of PHF8 significantly inhibited the proliferation, migration, and invasion of HCC cells. In addition, PHF8 was targeted by miR‐383 and its restoration rescued the inhibitory effect of miR‐383 on cell proliferation, migration, and invasion of HCC cells. Conclusion: miR‐383 could inhibit the proliferation, migration, and invasion of HCC cells by targeting PHF8, which will provide a basis for miR‐383 targeted therapy for HCC. [ABSTRACT FROM AUTHOR]