The　heterogeneity　of　hepatocellular　carcinoma　(HCC)　and　the　complexity　of　the　tumor　microenvironment　(TME)　pose　challenges　to　efficient　drug　delivery　and　the　antitumor　efficacy　of　combined　or　synergistic　therapies.　Herein,　a　metal-coordinated　carrier-free　nanodrug　(named　as　USFe3+　LA　NPs)　was　developed　for　ferroptosis-mediated　multimodal　synergistic　anti-HCC.　Natural　product　ursolic　acid　(UA)　was　incorporated　to　enhance　the　sensitivity　of　tumor　cells　to　sorafenib　(SRF).　Surface　decoration　of　cell　penetration　peptide　and　epithelial　cell　adhesion　molecule　aptamer　facilitated　the　uptake　of　USFe3+　LA　NPs　by　HepG2　cells.　Meanwhile,　Fe3+　ions　could　react　with　intracellular　hydrogen　peroxide,　generating　toxic　hydroxyl　radical　(·OH)　for　chemodynamical　therapy　(CDT)　and　amplified　ferroptosis　by　cystine/glutamate　antiporter　system　(System　Xc−),　which　promoted　the　consumption　of　glutathione　(GSH)　and　inhibited　the　expression　of　glutathione　peroxidase　4　(GPX4).　Notably,　these　all-in-one　nanodrugs　could　inhibit　tumor　metastasis　and　induced　immunogenic　cell　death　(ICD).　Last　but　not　least,　the　nanodrugs　demonstrated　favorable　biocompatibility,　augmenting　the　immune　response　against　the　programmed　death-ligand　1　(PD-L1)　by　increasing　cytotoxic　T　cell　infiltration.　In　vivo　studies　revealed　significant　suppression　of　tumor　growth　and　distant　metastasis.　Overall,　our　work　introduced　a　novel　strategy　for　applications　of　metal-coordinated　co-assembled　carrier-free　nano-delivery　system　in　HCC　combination　therapy,　especially　in　the　realms　of　cancer　metastasis　prevention　and　immunotherapy.　©　2024　Elsevier　Inc.