We constructed the significant high expression (fold change ≥ 2) cytosolic iron-sulfur protein assembly 1 (CIAO1) downstream activation of phospholipase A2 and hormone-mediated signaling-induced cell death network in human Hepato Cellular Carcinoma (HCC), compared with low expression no-tumor hepatitis/cirrhotic tissues (HBV or HCV infection) in GEO data set, by using integration of gene regulatory activated and inhibited network inference method. Our result showed that CIAO1 downstream activation of phospholipase A2 and hormone-mediated signaling-induced cell death upstream network had no result, and downstream CIAO1-activated PLA2G1B, NUP62 in HCC. By integrative analysis of biological processes simultaneous occurrence between the different CIAO1 activated downstream cell death gene ontology (GO) network of HCC compared with CIAO1 activated downstream cell death GO network of no-tumor hepatitis/cirrhotic tissues, and the same compared CIAO1 inhibited downstream cell death GO network of no-tumor hepatitis/cirrhotic tissues, or the different compared CIAO1 inhibited downstream cell death GO network of HCC, we proposed and verified that CIAO1 activated upstream network had no result; Downstream network consisted of activation of phospholipase A2, cell death, protein kinase cascade, regulation of signal transduction, hormonemediated signaling, negative regulation of epidermal growth factor receptor signaling pathway, negative regulation of MAPK (Mitogen Activated Protein Kinase) activity, negative regulation of Ras protein signal transduction in HCC, as a result of downstream activation of phospholipase A2 and hormone-mediated signaling-induced cell death in HCC.