Cells generate mass amount of EVs during ferroptosis. To evaluate the unique proteins secreted by ferroptitic EVs, and the potential mechnism of ferroptosis propagation through EV transportation,we analysed the proteomics of EVs from U-2 OS cells. U-2 OS cells were treated with DMSO or RSL3 (to induce ferroptosis) and EVs were collected from the culture medium.We further evaluated teh mice kidney derived EV proteomics and identified upregulated proteins in RSL3-treated mice. To elucidate the function of CD9-positive EVs, we generated wild type and CD9-KO HT1080 xenografts and treated the mice with RSL3 and enriched the xenograft EVs and performed proteomics analysis.