The present study aimed to explore the genetic changes involved in the liver hepatocellular carcinoma (HCC) development. The RNA-Seq data of 212 HCC tissue samples and 50 normal tissue samples were downloaded using TCGA-Assembler. A total of 4 subgroups were obtained, and 4167, 6279, 5379, and 2548 DEGs were screened in group 1, group 2, group 3, and group 4, respectively. Enrichment analysis found that cell cycle, metabolism, and translation related terms were the most significantly changed

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... ctions and pathways. There were 454 genes (1114 pairs), 803 genes (722 pairs), and 788 genes (724 pairs), separately interacted in the condition specific PPI network of group 1, 2, 3, and 4, with MMP2, ATNXN1, F2, and HDAC1 as the hub genes. What's more, using these genes, total 7, 20, 198, and 1 subtype related miRNAs; 35, 50, 47, and 17 subtype related TFs; 1, 1, 0, and 2 subtype related drugs were screened in group 1, 2, 3, and 4, respectively. The integrated biological analysis on RNA-Seq data provided substantial of bio-molecular related to the HCC development. miR-147b, SP1, and Riboflavin were the subtype-related regulator/drug for HCC. The study about the big data of HCC RNA-Seq data reveals the intrinsic gene expression pattern of the tumor, which provides a novel perspective to understand the heterogeneity of pathogenesis in HCC tumorigenesis.