Hepatocellular carcinoma (HCC) is a common and high-mortality cancer worldwide. Numerous microRNAs have crucial roles in the progression of different cancers. However, identifying the important microRNAs and the target biological function of the microRNA in HCC progression is difficult. In this study, we selected highly expressed microRNAs with different read counts as candidate microRNAs and then tested whether the microRNAs were differentially expressed in HCC tumour tissues, and we found that their expression was related to the HCC prognosis. Then, we investigated the effects of microRNAs on the cell growth and mobility of HCC using a real-time cell analyser (RTCA), colony formation assay and subcutaneous xenograft models. We further used deep-sequencing technology and bioinformatic analyses to evaluate the main functions of the microRNAs. We found that miR-103a was one of the most highly expressed microRNAs in HCC tissues and that it was upregulated in HCC tissue compared with the controls. In addition, high miR-103a expression was associated with poor patient prognosis, and its overexpression promoted HCC cell growth and mobility. A functional enrichment analysis showed that miR-103a mainly promoted glucose metabolism and inhibited cell death. We validated this analysis, and the data showed that miR-103a promoted glucose metabolism-likely function and directly inhibited cell death via ATP11A and EIF5. Therefore, our study revealed that miR-103a may act as a key mediator in HCC progression.