MicroRNAs have been verified to participate in various biological behaviors of different tumors, via multiple signaling pathways. Many kinds of microRNAs in hepatocellular carcinoma have been researched. However, miR-30b-5p hasn't been included. Our study aim at the impacts of miR-30b-5p on HCC and the pathway it mediating. The results showed miR-30b-5p was significant downregulated in HCC tissues and cell lines. With clinical data, we've discovered miR-30b-5p was correlated with several clinical pathological characteristics, such as survival time, tumor size, HBV infected, pathological stage, differentiation and intrahepatic metastasis. Also we illustrated miR-30b-5p repressed cell proliferation and cell cycle of HCC cell lines. For a further study, we figured out that miR-30b-5p mediated DNMT3A to repress proliferation, meanwhile it targeted USP37 for decelerating cell cycle. This discovery inferred miR-30b-5p a potential favorable biomarker and therapeutic target for HCC diagnosis and treatment.