Background Many recent studies have reported the role of WGCNA in liver cancer, and screened out modules related to the clinical characteristics of liver cancer. The prognostic role of modular genes provides a reference for the treatment of liver cancer and the study of survival time extension. MethodsUse edgeR to screen differentially expressed genes, and use weighted gene co-expression network analysis (WGCNA) method to divide differential genes into modules; combined with clinical data, select gene modules that are highly related to clinical information to construct a prognostic model. Use univariate Cox and multivariate Cox regression analysis to predict the value of prognosis. The Kaplan-Meier method and ROC curves were used to evaluate the value of features of predicting prognosis.ResultsIn the co-expression analysis of liver cancer, the two gene modules darkrey and navajowhite2 was highly correlated with the TNM stag of liver cancer. In addition, they were related to the reduction process and the activation of specific DNA-binding transcription factors. Constructing a risk ratio model with these two modules shows that the overall survival time of patients in the high-risk group is lower than that of the low-risk group. In the module, ABLIM2, RP11-109J4.1, TXNRD1, C9orf106, LINC00677, CYP11B2, AC005550.3 and MIR3945HG belong to the Hub gene, and can also be used as independent prognostic factors, which may become potential biomarkers for the diagnosis and treatment of liver cancer. Conclusion This studies identified and screened the prognostic genes RP11-109J4.1, TXNRD1, C9orf106, LINC00677, CYP11B2, AC005550.3 and MIR3945HG related to the progression of liver cancer, which can provide a reference form the diagnosis and treatment of liver cancer.