The findings showed: (1) I/R‐induced AKI enhances ferroptosis; (2) Elevated HIF‐1α expression in the I/R group; (3) HIF‐1α antagonises ferroptosis through SLC7A11; (4) HIF‐1α prevents the onset of apoptosis and ferroptosis; (5) HIF‐1α knockout aggravates ferroptosis; (6) Overexpression of iASPP inhibits ferroptosis; (7) Inhibition of iASPP expression can promote ferroptosis; (8) HIF‐1α‐mediated I/R‐induced AKI is dependent on the SLC7A11/GPX4 signalling pathway. This evidence concerns the gene GPX4 and acute kidney injury.