Abstract: Objective To prepare mitochondria-targeted buquinar(BQR) liposome (BQR@MLipo), and evaluate its capacity to induce ferroptosis in human renal cell carcinomas ACHN cells.Methods BQR@MLipo was prepared using the thin-film dispersion method. The encapsulation efficiency was used as an evaluation indicator to optimize the formulation of BQR@MLipo,followed by characterization. Furthermore, the antitumor effect of BQR@MLipo was investigated through cellular intake analysis and cellular survival determination. Then, mitochondrial reactive oxygen species (mtROS) content determination, detection of oxidized glutathione/reduced glutathione (GSSG/GSH) ratio, and lipid hydroperoxide (LPO) content determination were performed to assess the capacity of BQR@MLipo to induce ferroptosis in ACHN cells.Results According to the optimal prescription, BQR@MLipo had a diameter of (95.03±1.93) nm, a Zeta potential of (4.44±0.48) mV, and an encapsulation efficiency of (65.37±1.88)%. BQR@Lipo had an average particle size of (92.45±2.45) nm, a Zeta potential of (-20.70±0.92) mV, and an encapsulation efficiency of (73.05±1.40)%. Furthermore, BQR@MLipo successfully accumulated in the mitochondria and disrupted the redox system in ACHN cells, leading to the accumulation of lipid peroxides and ferroptosis. Compared with BQR@Lipo or BQR, BQR@MLipo exhibited strongest ability to kill ACHN cells.Conclusions BQR@MLipo is successfully prepared, which significantly induces mitochondria-related ferroptosis in ACHN cells.