Objective To investigate the mechanism of iron death induced by dihydroartemisinin (DHA)/artesunate (ARTS) in kidney cancer cell line 786-0. Methods After DHA/ARTS stimulated kidney cancer cell line 786-0, the renal cancer cell death induced by DHA/ARTS was determined as iron death. The changes of NCOA4 and FTH1 after DHA/ARTS were observed by RT-qPCR and Western blot. The effects of DHA/ARTS on 786-0 were observed after NCOA4 was knocked down by two different siRNA. The plasmid pmCherry EGFP FTH1 was constructed and overexpressed. The changes of fluorescence color and brightness after DHA/ARTS were observed to determine the autophagy degradation of FTH1. After NCOA4 was deleted, pmCherry-GFP-FTH1 plasmid was transfected. The fluorescence color and brightness of DHA/ARTS were detected, and the autophagy degradation of FTH1 was regulated by NCOA4. Results 786-0 cell line treated with DHA and ARTS, the cell death was observed by microscope and CCK-8, and the number of viable cells decreased with the increase of drug concentration. The lethal effects of DHA and ARTS could be inhibited by iron death inhibitors DFO and Fer-1. The fluorescence intensity of ROS in 786-0 cells under DHA and ARTS was significantly higher than that in control group, and the difference was statistically significant (2. 894,2 .342; P＜0.05). The fluorescence intensity of ROS in 786-0 cells of DHA+DFO, DHA+ Fer-1, ARTS+DFO, ARTS+ Fer-1 group was significantly lower than that of DHA and ARTS group (P＜0.05). The autophagy rates of DHA and ARTS groups were significantly higher than those of control group (P＜0.05), and the autophagy rates of 50μM DHA and ARTS groups were significantly higher than those of 20μM DHA and ARTS groups (P＜0.05). After NCOA4 expression was silenced by siRNA-NCOA4, autophagy rate was significantly decreased (P＜0.05). Conclusion Artemisinin derivatives DHA and ARTS can induce iron death in 786-0 renal cancer cell lines, which is realized by NCOA4 mediated specific autophagy degradation of FTH1.