Our investigation indicated that (i) Lip-1 suppressed ferroptosis of renal tubular cell in I/R-induced AKI; (ii) EGR1 might be a key regulator of ferroptosis in I/R-induced AKI; (iii) Lip-1 inhibited ferroptosis of renal tubular cell via regulating EGR1/TP53/SLC7A11; and (iv) Lip-1 reduced infiltration of macrophages and release of inflammatory cytokines. Here, TP53 is linked to acute kidney injury.