Objective To investigate the expression and effect of miR-150-5p on cell proliferation, cell apoptosis and cell cycle in human hepatocellular carcinoma cells. Methods The expression of miR-150-5p in hepatocellular carcinoma cells and normal human liver cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Proliferation of hepatocellular carcinoma cells was analyzed by MTT. Cell apoptosis and cell cycle of hepatocellular carcinoma cells were analyzed by flow cytometry. Luciferase assay was performed to detect whether ZNF609 was the direct target of miR-150-5p in the hepatocellular carcinoma cells. Results The expression of miR-150-5p was significantly down regulated in the hepatocellular carcinoma cells compared to the normal human liver cells. Proliferation of the hepatocellular carcinoma cells was significantly inhibited by miR-150-5p, but cell apoptosis was significantly promoted. Cell cycle of the hepatocellular carcinoma cells was arrested at G1 phage after transfection of miR-150-5p mimics. Further investigation proved ZNF609 was the direct target of miR-150-5p in hepatocellular carcinoma cells. Conclusions miR-150-5p may function as tumor suppressor and play important roles in cell proliferation, cell apoptosis and cell cycle in hepatocellular carcinoma cells by directly targeting ZNF609.