Liver fibrosis is the result of long-term liver injury and has a high incidence worldwide. Protocatechuic acid (PCA) is ubiquitous in vegetables, nuts, brown rice and herbal medicines, which is reported to possess anti-asthmatic, anti-cancer, and anti-oxidation properties. Our research aimed to investigate the effect of PCA on liver fibrosis. , TNF-α-induced hepatic stellate cell (HSC) model was used to assess the anti-fibrosis effects of PCA. , mice were treated with thioacetamide (TAA) to develop liver fibrosis. Body weight, organ index, histological changes, and proteins alteration of factors associated with TGF-β signaling pathway were used to assess the anti-fibrosis effects of PCA. Our results showed that PCA not only inhibited cell viability in TNF-α activated HSC-T6 cells , but also efficiently mitigated TAA-induced liver damage and fibrosis . Further experiments indicated that PCA played a protective role in liver fibrosis through regulation of the TGF-β signaling pathway downregulating the protein expression of p-Smad2, p-ERK, c-Jun. In summary, our findings provide a pharmacological justification for the clinical application of PCA in preventing or treating liver fibrosis.