Liver fibrosis (LF) is a kind of progressive liver injury reaction. The goal of this study was to achieve a more detailed understanding of the molecular changes in response to CCl4-induced LF through the identification of a differentially expressed liver proteomic. A total of 302 differentially expressed proteins (DEPs) were significantly identified at the proteomic level. Importantly,Gstm1, Gstm3, Ephx1 and Gstp1 were shown to be associated with metabolic pathways, and parallel reaction monitoring (PRM) verification showed that the results were consistent with those of data -independent acquisition (DIA). Through the analysis of proteomic data, this study provides valuable insights into the potential mechanism of the pathogenesis of LF, and lays a theoretical foundation for the further development of targeted therapy for LF.