Objective To analyze the differentially expressed gene profiling during the development from chronic hepatitis C to HCC. Method The research uses the gene expression profile data GDS4880 and GDS4887 of the GEO database as the analysis material to make screening of the differential expression genes of the chronic hepatitis C and the HCV related HCC’s microarray data by using Qlucore Omics Explorer software, and analyze the differential expression genes and their interaction relations by using the bioinformatics tools PANTHER, DAVID , STRING and Cytoscape. Results 328 differentially-expressed genes were screened out(133 with upward effects and 195 with downward effects). The relevant genes were mainly involved in biological pathways such as metabolic process,biological regulation,localization,p53 signaling pathway, phosphatidylinositol signaling system, insulin signaling pathway, apoptosis, etc. The interaction between encoded proteins of the differential expression gene mainly focuses on the 14 proteins（CYP2B6、CYP2E1、AKT1、CDK16、RELA、CDC27、PIK3CA、GNB1、FOXO1、FYN、PDPK1、SCAND1、SGOL1、RPH3AL）Conclusion The 14 genes may be associated with the development of HCV-related hepatocellular carcinoma.