Blocking ROS or p53 reversed these effects, confirming a ROS-p53-SLC7A11/GPX4 feedback loop.<h4>Conclusion</h4>ACSL1 functions as a tumor suppressor in ccRCC by inducing ferroptosis via the ROS-p53-SLC7A11/GPX4 axis. This evidence concerns the gene TP53 and nonpapillary renal cell carcinoma.