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Background: Our aim is to study novel high expression activated PTHLH feedback network-mediated regulation of cell growth mechanism in HCC.Methods: We studied the different biological processes and occurrence numbers between high expression (fold change >2) activated PTHLH feedback network-mediated regulation of cell growth gene ontology (GO) network of human hepatocellular carcinoma (HCC) compared with the corresponding low expression activated GO network of no-tumor hepatitis/cirrhotic tissues (HBV or HCV infection).We constructed activated PTHLH coupling feedback microtubule cytoskeleton organization to nucleic acid metabolism-induced regulation of cell growth network from GEO data set using gene regulatory network inference method and our programming.Results: Activated PTHLH feedback network-mediated regulation of cell growth network consisted of DNA repair, microtubule cytoskeleton organization and biogenesis, nucleotide and nucleic acid metabolism, oxidation reduction, protein modification, proteolysis, regulation of cell growth in HCC.Activated PTHLH coupling feedback microtubule cytoskeleton organization to nucleic acid metabolism-induced regulation of cell growth network included upstream MAPT, TK1, ESM1, and downstream ESM1, TUBG1, TK1 in HCC.Conclusions: We proposed activated PTHLH coupling feedback microtubule cytoskeleton organization to nucleic acid metabolism-induced regulation of cell growth network.Our hypothesis was verified by the same activated PTHLH feedback network-mediated regulation of cell growth GO network of HCC with the corresponding inhibited GO network of no-tumor hepatitis/cirrhotic tissues, or the different with the corresponding inhibited GO network of HCC .