Children　with　extracranial　high-risk　neuroblastoma　(NB)　have　a　poor　prognosis　due　to　resistance　against　apoptosis.　Recently,　ferroptosis,　another　form　of　programmed　cell　death,　has　been　tested　in　clinical　trials　for　high-risk　NB;　however,　drug　resistance　and　side　effects　have　also　been　observed.　Here,　we　find　that　the　gold　element　in　gold　nanoclusters　can　significantly　affect　iron　metabolism　and　sensitize　high-risk　NB　cells　to　ferroptosis.　Accordingly,　we　developed　a　gold　nanocluster　conjugated　with　a　modified　NB-targeting　peptide.　This　gold　nanocluster,　namely,　NANT,　shows　excellent　NB　targeting　efficiency　and　dramatically　promotes　ferroptosis.　Surprisingly,　this　effect　is　exerted　by　elevating　the　noncanonical　ferroptosis　pathway,　which　is　dependent　on　heme　oxygenase-1-regulated　Fe(II)　accumulation.　Furthermore,　NANT　dramatically　inhibits　the　growth　of　high-risk　NB　in　both　tumor　spheroid　and　xenograft　models　by　promoting　noncanonical　ferroptosis　evidenced　by　enhanced　intratumoral　Fe(II)　and　heme　oxygenase-1.　Importantly,　this　strategy　shows　excellent　cardiosafety,　offering　a　promising　strategy　to　overcome　ferroptosis　resistance　for　the　efficient　and　safe　treatment　of　children　with　high-risk　neuroblastoma.