A cyclopentadienyl Ir(iii) complex with natural product betulin, Ir13, activated the ferroptosis cascade through ferritinophagy and iron homeostasis regulation.237Ir13 activated PERK/eIF2α pathway and CRT exposure, and HMGB1 and ATP release were detected in vitro in A549 cancer cells. The gene discussed is HMGB1; the disease is cancer.