Objective: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases, including a series of pathological changes, from benign nonalcoholic fatty liver (NAFL), nonalcoholic steatohepatitis (NASH), liver cirrhosis, and finally to hepatocellular carcinoma. The purpose of this study was to construct a gene co-expression network by using weighted gene co-expression network analysis (WGCNA) to explore the potential key pathways and genes in the genesis and development of NASH. Methods: Data were collected from two data sets GSE48452 and GSE89632 in the Gene Expression Omnibus (GEO) database. WGCNA was used to identify NASH-related modules. The potential biological functions of NASH were discussed by functional enrichment analysis. These genes were analyzed with protein-protein interactions. Results: The black module in GSE48452 data set and gray module in GSE89632 data set had the most significant correlation with NASH. The enrichment analysis of Gene Ontology (GO) showed that the biological functions of the target gene focused on lipid degradation, nuclear chromosome, and organic acid binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway showed that genes were enriched in peroxisome proliferator-activated receptor (PPAR) pathway. Conclusion: Through WGCNA analysis, the potential genes [lipoprotein lipase (LPL), thymidylate synthetase (TYMS), cytochrome P450 family 26 subfamily A member 1 (CYP26A1), fatty acid-binding protein 4 (FABP4), fatty acid-binding protein 5 (FABP5), minichromosome maintenance protein 2 (MCM2), minichromosome maintenance protein 5 (MCM5), GINS complex subunit 2 (GINS2)] and key pathways related to NASH have been identified. These genes may be involved in the transformation process from NAFL to NASH and have certain diagnostic and therapeutic value.