Traditional　cancer　chemotherapy　suffers　from　low　efficacy　and　severe　side　effects,　limiting　its　use　as　a　first-line　treatment.　To　address　this　issue,　we　investigated　a　novel　way　to　induce　lipid　peroxidation　(LPO),　which　plays　an　essential　role　in　ferroptosis　and　may　be　useful　against　cancer　cells　and　tumors.　In　this　study,　a　pH-responsive　synergistic　cancer　therapy　nanoplatform　was　prepared　using　CaCO3　co-loaded　with　oleanolic　acid　(OA)　and　lipoxygenase　(LOX),　resulting　in　the　formation　OLCaP　NP.　This　nanoplatform　exhibited　good　drug　release　properties　in　an　acidic　tumor　environment　owing　to　the　presence　of　CaCO3　.　As　a　result　of　acidic　stimulation　at　tumor　sites,　the　OLCaP　NP　released　OA　and　LOX.　OA,　a　chemotherapeutic　drug　with　anticancer　activity,　is　already　known　to　promote　the　apoptosis　of　cancer　cells,　and　LOX　is　a　natural　enzyme　that　catalyzes　the　oxidation　of　polyunsaturated　fatty　acids,　leading　to　the　accumulation　of　lipid　peroxides　and　promoting　the　apoptosis　of　cancer　cells.　More　importantly,　OA　upregulated　the　expression　of　acyl-coenzyme　A　synthetase　long-chain　family　member　4　(ACSL4),　which　promoted　enzyme-mediated　LPO.　Based　on　our　combined　chemotherapy　and　nanocatalytic　therapy,　the　OLCaP　NP　not　only　had　remarkable　antitumor　ability　but　also　upregulated　ACSL4　expression,　allowing　further　amplification　of　LPO　to　inhibit　tumor　growth.　These　findings　demonstrate　the　potential　of　this　nanoplatform　to　enhance　the　therapeutic　efficacy　against　tumors　by　inducing　oxidative　stress　and　disrupting　lipid　metabolism,　highlighting　its　clinical　potential　for　improved　cancer　treatment.