Abstract: This study aims to illustrate the crucial genes and potential mechanism in the occurrence and develop-ment of liver fibrosis via weighted gene co-expression network analysis（WGCNA）. The whole genome ex-pression data of patients with liver fibrosis（GSE84044） were derived from GEO database.WGCNA was conducted to estimate the crucial models and genes correlated with development of liver fibrosis. GO functional annotations and KEGG pathway enrichment were further applied for the investigation of potential mechanism. A total of 22 876 genes were clustered into 8 modules by WGCNA, two modules of which were identified as significantly correlated with liver fibrosis. GO annotation and KEGG enrichment results showed that these two modules were mainly related to the production of extracellular matrix and collagen. Analysis of crucial genes of WGCNA in the four stages of liver fibrosis showed that top ten genes, including LIPC, DCN, LUM and COL1A1, were identified as differentially expressed during the development of liver fibrosis. In this study, WGCNA was used to analyze the gene chip of patients with liver fibrosis, to dig out the important genes in the process of liver fibrosis, and to provide a new screening direction of biomarkers and potential targets for the prevention and treatment of liver fibrosis.