Background and aim: Hepatocellular carcinoma (HCC) is a major cause of cancer mortality and is increasing incidence worldwide. The aim of this study was to identify the key genes and microRNAs in HCC and explore their potential mechanisms. 
Methods: The gene expression profiles of GSE76427, GSE64041, GSE57957, and the microRNA dataset GSE67882 were downloaded from the Gene Expression Omnibus database. The online tool GEO2R was used to obtain differentially expressed genes (DEGs) and miRNAs (DEMs). The gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed for DEGs using the Database for Annotation, Visualization, and Integrated Discovery. A protein–protein interaction (PPI) network of the DEGs was constructed by Search Tool for the Retrieval of Interacting Genes and visualized by Cytoscape. Moreover, miRecords was used to predict the target genes of DEMs. 
Results: In total, 106 DEGs were screened out in HCC, consisting of 89 upregulated genes and 17 downregulated genes, which were mainly enriched in biological processes associated with oxidation–reduction process. Besides, the Kyoto Encyclopedia of Genes and Genomes pathways including chemical carcinogenesis, drug metabolism-cytochrome P450, tryptophan metabolism, and retinol metabolism were involved. A PPI network was constructed consisting of 105 nodes and 66 edges. A significant module including nine hub genes, ASPM, AURKA, CCNB2, CDKN3, MELK, NCAPG, NUSAP1, PRC1, and TOP2A, was detected from the PPI network by Molecular Complex Detection. The enriched functions were mainly associated with the mitotic cell cycle process, cell division, and mitotic cell cycle. In addition, a total of 21 DEMs were identified, including 9 upregulated and 12 downregulated miRNAs. Interestingly, ZBTB41 was the potential target of seven miRNAs. Finally, the nine hub genes and three miRNA-target genes expression levels were validated by reverse transcription-polymerase chain reaction. The relative expression levels of nine genes (ASPM, AURKA, CDKN3, MELK, NCAPG, PRC1, TOP2A, ZBTB41, and ZNF148) were significantly upregulated in cancer tissues. 
Conclusion: This study identified the key genes and potential molecular mechanisms underlying the development of HCC, which could provide new insight for HCC interventional strategies.
Keywords: hepatocellular carcinoma, bioinformatic analysis, differentially expressed genes, differentially expressed microRNAs