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Aim: This study aimed to investigate the key transcription factors (TFs), long noncoding RNAs (lncRNAs), and microRNAs (miRNAs) associated with hepatocellular carcinoma (HCC).Materials and Methods: The datasets GSE31383 and GSE54238 were downloaded from Gene Expression Omnibus data repository. GSE31383 was used to screen differentially expressed miRNAs, and GSE54238 was used to screen differentially expressed messenger RNAs (mRNAs) and lncRNAs. ChipBase was used to identify TF-miRNA pairs. StarBase was selected to identify miRNA-mRNA and lncRNA-miRNA interactions. Kyoto Encyclopedia of Genes and Genomes pathway analysis was also conducted using Database for Annotation, Visualization, and Integrated Discovery tool.Results: A total of 2065 mRNAs, 1050 lncRNAs, and 26 miRNAs were identified to be divergently expressed in HCC compared with normal tissues. There were 338 miRNA-mRNA and 65 lncRNA-miRNA pairs with reverse expression trend. Besides 249 TF-miRNA relationships including differentially expressed miRNA were isolated. Among them, 11 TF-miRNA had the same expression trend. Furthermore, lncRNA-miRNA-mRNA and TF-miRNA-mRNA regulatory networks were constructed. hsa-miR-497, hsa-miR-195, and hsa-miR-424 were identified as hub nodes in these two networks. Hub TFs, such as TATA box binding protein-associated factor 1 (TAF1) and hepatocyte nuclear factor 4, alpha (HNF4α), and lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) were also screened out in the network.Conclusions: Our findings highlight the regulatory networks among TFs, lncRNAs, miRNAs, and mRNAs in HCC. Several key molecules, such as hsa-miR-195, lncRNA MALAT1 and TFs TAF1 and HNF4α, may contribute to the progression of HCC. [ABSTRACT FROM AUTHOR]