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Background: Hepatocellular carcinoma (HCC) is the most common type of liver tumour, and is closely related to liver cirrhosis. Previous studies have focussed on the pathogenesis of liver cirrhosis developing into HCC, but the molecular mechanism remains unclear. The aims of the present study were to identify key genes related to the transformation of cirrhosis into HCC, and explore the associated molecular mechanisms.Methods: GSE89377, GSE17548, GSE63898 and GSE54236 mRNA microarray datasets from Gene Expression Omnibus (GEO) were analysed to obtain differentially expressed genes (DEGs) between HCC and liver cirrhosis tissues, and network analysis of protein-protein interactions (PPIs) was carried out. String and Cytoscape were used to analyse modules and identify hub genes, Kaplan-Meier Plotter and Oncomine databases were used to explore relationships between hub genes and disease occurrence, development and prognosis of HCC, and the molecular mechanism of the main hub gene was probed using Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis.Results: In total, 58 DEGs were obtained, of which 12 and 46 were up- and down-regulated, respectively. Three hub genes (CDKN3, CYP2C9 and LCAT) were identified and associated prognostic information was obtained. CDKN3 may be correlated with the occurrence, invasion, and recurrence of HCC. Genes closely related to changes in the CDKN3 hub gene were screened, and Kyoto Encyclopedia of Genes and Genomes (KEGGs) pathway analysis identified numerous cell cycle-related genes.Conclusion: CDKN3 may affect the transformation of liver cirrhosis into HCC, and represents a new candidate molecular marker of the occurrence and progression of HCC. [ABSTRACT FROM AUTHOR]