AIM: To investigate the effect of liquorice extract on TGF-β1-induced myocardial fibroblast (CFs) fibrosis. METHODS: 10 ng/mL TGF-β1 induced CFs to establish myocardial fibrosis cell model. Fibrotic cells were treated with liquorice extract and the cell activity was detected by MTT assay. CCK-8 was used to detect the effect of liquorice extract on CFs proliferation. The expression of smooth muscle actin (α-SMA) was detected by immunofluorescence. Western blot was used to detect TGF-β1/Smad signaling pathway related proteins and p-Smad2, p-Smad3 expression levels. The mRNA expression levels of Smad2, Smad3 and Smad4 were detected by RT-PCR. RESULTS: Compared with the control group, there were statistically significant differences in cell activity (P<0.05). The cell proliferation rate of glycyrrhiza uralensis extract groups was significantly lower than that of TGF-β1 group (P<0.05). The expression levels of α-SMA and TGF-β1/Smad signaling pathway related proteins in 100 μg/mL liquorice extract were significantly lower than those in TGF-β1 group (P<0.05). CONCLUSION: Glycyrrhiza extract can improve the occurrence and development of TGF-β1-induced myocardial fibrosis, and its mechanism maybe related to the inhibition of TGF-β1/Smad signaling pathway.