Follistatin‑like 1 (Fstl1) is a secreted glycoprotein that belongs to the follistatin and SPARC (secreted protein, acidic and rich in cysteine) families and was identified to serve a critical role in lung fibrosis. However, the role of Fstl1 in liver fibrosis remains undefined. Therefore, the aim of the present study was to investigate the role of Fstl1 in liver fibrosis. The results indicated that Fstl1 was highly expressed in human hepatic fibrosis tissues and activated hepatic stellate cells (HSCs). Furthermore, knockdown of Fstl1effectively suppressed HSC proliferation and the protein expression levels of α‑SMA and collagen I in transforming growth factor (TGF)‑β1‑treated HSCs. Mechanistically, knockdown of Fstl1 remarkably decreased the phosphorylation level of Smad3 in TGF‑β1‑induced HSCs. Taken together, the present study demonstrated that Fstl1serves an important role in liver fibrosis and target deletion of Fstl1 attenuated HSCs activation through suppressing TGF‑β1/Smad3 signaling pathway. Therefore, Fstl1 may be a potential therapeutic target for the treatment of liver fibrosis.