Matrine, one of the active ingredients of Sophora flavescens Ait., has a protective effect in animal models on acute liver injury and liver fibrosis. However, since the protective effects are short-lived, a structural modification of matrine is needed to improve its anti-fibrotic effects. In the previous study we obtained a stable, highly active new matrine derivative, WM130, and explored its anti-fibrotic effects on the human hepatic stellate cell line, LX-2. CCK-8, wound healing, and transwell assays were used to investigate cell proliferation and migration, while 3D mimic study was used to determine the target of WM130. Western blots investigated the levels of α-SMA, cofilin 1, p-cofilin 1, F-actin, PI3K, p-Akt, Akt, and PTEN in LX-2 cells treated with MW130. The results revealed that WM130 can significantly inhibit the proliferation of LX-2 cells at an IC50 of 60 μg/ml. At 30 µg/ml, matrine or WM130 significantly inhibited the migration of LX-2 cells. Moreover, WM130 significantly reduced the expression of α-SMA, cofilin 1, F-actin, PI3K, and p-Akt, and increased PTEN levels. In conclusion, WM130 inhibits the proliferation, activation, and migration of human hepatic stellate LX-2 cells by targeting cofilin 1. © 2022, The Author(s), under exclusive licence to Springer Nature B.V.