Recently, nanozymes with peroxidase (POD)-like activity have shown great promise for ferroptosis-based tumor therapy, which are capable of transforming hydrogen peroxide (HO) to highly toxic hydroxyl radicals (OH). However, the unsatisfactory therapeutic performance of nanozymes due to insufficient endogenous HO and acidity at tumor sites has always been a conundrum. Herein, an ultrasmall gold (Au) @ ferrous sulfide (FeS) cascade nanozyme (AuNP@FeS) with HS-releasing ability constructed with an Au nanoparticle (AuNP) and an FeS nanoparticle (FeSNP) is designed to increase the HO level and acidity in tumor cells the collaboration between cascade reactions of AuNP@FeS and the biological effects of released HS, achieving enhanced OH generation as well as effective ferroptosis for tumor therapy. The cascade reaction in tumor cells is activated by the glucose oxidase (GOD)-like activity of AuNP in AuNP@FeS to catalyze intratumoral glucose into HO and gluconic acid; meanwhile, the released HS from AuNP@FeS reduces HO consumption by inhibiting intracellular catalase (CAT) activity and promotes lactic acid accumulation. The two pathways synergistically boost HO and acidity in tumor cells, thus inducing a cascade to generate abundant OH by catalyzing HO through the POD-like activity of FeS in AuNP@FeS and ultimately causing amplified ferroptosis. and experiments demonstrated that AuNP@FeS presents a superior tumor therapeutic effect compared to that of AuNP or FeS alone. This strategy represents a simple but powerful method to amplify ferroptosis with HS-releasing cascade nanozymes and will pave a new way for the development of tumor therapy.