Liver fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM), which is primarily produced by activated hepatic stellate cells (HSCs). However, effective therapies for hepatic fibrosis are currently lacking. Artesunate is a promising anti-fibrotic drug candidate, but its clinical application is hindered by limited absorption. Here, we present a novel oral delivery platform that enhances the HSCs uptake of artesunate and induces potent ferroptosis. The platform is vitamin A-decorated nanoparticles encapsulated with artesunate. The multifunctional ligand vitamin A interacts with retinol-binding proteins that are highly expressed on the intestinal epithelium to promote transcytosis, highly expressed on the surface of HSCs but lowly expressed in normal hepatocytes. After oral administration, this oral delivery platform enhances transepithelial transport in the intestine, improves drug accumulation in the liver, and continuously increases HSCs uptake of artesunate. Upon drug release in HSCs, artesunate depletes glutathione peroxidase 4 and glutathione, effectively initiating ferroptosis. In vivo experiments demonstrate that this strategy induces pronounced ferroptosis, efficiently relieving liver fibrosis. This work provides a proof-of-concept demonstration that an oral delivery strategy for ferroptosis inducers may be beneficial for liver fibrosis treatment.