In summary, our results demonstrate an important role for ACSL3-mediated lipid metabolism in driving a hallmark metabolic phenotype of ccRCC, the accumulation of lipid droplets, and that ACSL3-dependent lipid accumulation maintains ccRCC cell viability while simultaneously sensitizing cells to ferroptotic cell death, making it a compelling therapeutic target for the treatment of ccRCC. Here, ACSL3 is linked to nonpapillary renal cell carcinoma.