摘要Developing and identifying effective medications and targets for treating hepatic fibrosis is an urgent priority.Our previous research demonstrated the efficacy of artesunate(ART)in alle-viating liver fibrosis by eliminating activated hepatic stellate cells(HSCs).However,the un-derlying mechanism remains unclear despite these findings.Notably,endocytic adaptor pro-tein(NUMB)has significant implications for treating hepatic diseases,but current research primarily focuses on liver regeneration and hepatocellular carcinoma.The precise function of NUMB in liver fibrosis,particularly its ability to regulate HSCs,requires further investigation.This study aims to elucidate the role of NUMB in the anti-hepatic fibrosis action of ART in HSCs.We observed that the expression level of NUMB significantly decreased in activated HSCs compared to quiescent HSCs,exhibiting a negative correlation with the progression of liver fibrosis.Additionally,ART induced senescence in activated HSCs through the NUMB/P53 tumor suppressor(P53)axis.We identified NUMB as a crucial regulator of senescence in ac-tivated HSCs and as a mediator of ART in determining cell fate.This research examines the specific target of ART in eliminating activated HSCs,providing both theoretical and experi-mental evidence for the treatment of liver fibrosis.