Objective: To investigate the relationship between primary hepatocellular carcinoma (HCC) and the expression of circadian genes. Methods: The profiles containing 424 samples were downloaded from The Cancer Genome Atlas (TCGA) of the United States

including 374 cases of hepatoma samples and 50 cases of normal samples. Fifty-one circadian genes were analyzed by DECenter

so as to obtain the differentially expressed genes (DEGs). The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments of DEGs were performed by DAVID online analyses. The protein-protein interaction (PPI) networks of the DEGs were constructed through the STRING database. The circadian genes were studied on its main role in the occurrence and development of HCC. Results: A total of 51 DEGs were identified from 374 cases

among which 21 genes were upregulated (P<0.05) and 3 genes were downregulated (P<0.05). DEGs were mainly involved in the Wnt signaling pathway

Hedgehog signaling pathway and Hippo signaling pathway (P<0.001). Ten DEGs involving in circadian rhythm and regulation of metabolic process were closely associated in the PPI network (P<0.001). GO analysis showed that the biological functions of DEGs focused primarily on circadian rhythm

regulation of metabolic process and regulation of gene expression (P<0.001). Conclusion: DEGs participate in the development of primary HCC through the pathway of circadian rhythm and cell metabolism.