Caveolin-1 (Cav-1), as a membrane protein involved in the formation of caveolae, binds steroid receptors and endothelial nitric oxide synthase, limiting its translocation and activation. In the present study, we investigated the role of Cav-1 in the progression of hepatic fibrosis induced by carbon tetrachloride (CCl) in murine animals. Therefore, the wild type (WT) and Cav-1-knockout (Cav-1) mice were used in our study and subjected to CCl. The results indicated that CCl induced the decrease of Cav-1 expression in liver tissue samples. And Cav-1 intensified CCl-triggered hepatic injury, evidenced by the stronger hepatic histological alterations, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and liver terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells. CCl led to oxidative stress, supported by the reduced superoxide dismutase (SOD) activity and glutathione (GSH) levels, as well as enhanced malondialdehyde (MDA) and O levels in liver samples. And the process was intensified by Cav-1. Additionally, CCl-caused hepatic inflammation was aggregated by Cav-1 via further increasing the secretion of pro-inflammatory cytokines. Moreover, CCl-caused fibrosis was strengthened by Cav-1, which was evidenced by the up-regulation of α-smooth muscle actin (α-SMA), collagen alpha 1 type 1 (Col1A1), lysyl oxidase (Lox) and transforming growth factor-β1 (TGF-β1) in liver tissues. Similar results were observed in TGF-β1-stimulated hepatic stellate cells (HSCs) and LX-2 cells without Cav-1 expressions that in vitro, suppressing Cav-1 further accelerated TGF-β1-induced oxidative stress, inflammation and fibrosis development. In conclusion, our results indicated that Cav-1 played an important role in CCl-induced hepatic injury, which may be used as potential therapeutic target for hepatic fibrosis treatment.