Platinum　chemotherapy　drugs,　represented　by　cisplatin,　have　been　widely　used　in　cancer　therapy.　While　they　are　effective,　their　use　is　limited　by　their　adverse　effects　in　long-term　administration,　especially　the　lack　of　selectivity　and　high　systemic　toxicity.　Encouragingly,　molecular-like　platinum　nanoclusters,　as　a　bridge　between　nanomedical　and　small　molecular　drugs,　provide　an　attractive　opportunity　to　completely　change　the　current　status　of　cancer　treatment,　mainly　due　to　their　unique　structural　advantages,　making　them　highly　efficient　and　low　toxic.　Functional　modifications　offer　a　promising　avenue　to　enhance　template-modified　platinum　nanoclusters＇　selectivity　and　safety,　addressing　systemic　toxicity　concerns.　Concurrently,　leveraging　tumor　heterogeneity　facilitates　drug　bioactivity　via　metabolism,　thereby　augmenting　therapeutic　efficacy.　Herein,　we　utilized　iRGD-modified　bovine　serum　albumin　(BSA-iRGD)　as　the　protective　molecule　to　construct　platinum　nanoclusters　drug　(PtNC@BSA-iRGD)　directly　under　mild　conditions.　The　new　type　of　chemotherapeutic　drug　PtNC@BSA-iRGD　exhibits　excellent　antitumor　activity　in　vitro/vivo,　in　comparison　to　clinical　commercial　first-line　carboplatin.　This　powerful　antitumor　effect　is　attributed　to　its　selective　uptake　by　tumor　cells　through　receptor-mediated　endocytosis.　The　release　of　platinum　ions　inhibits　DNA　replication　by　forming　DNA-Pt　complexes,　activates　apoptosis　pathways,　and　ultimately　induces　tumor　cell　apoptosis.　More　impressively,　compared　to　first-line　platinum　chemotherapy　drugs,　PtNC@BSA-iRGD　has　superior　biocompatibility　while　possessing　higher　tumor　inhibitory　activity　in　vivo　during　medication　treatment.　This　feature　compensates　for　the　shortcomings　of　clinical　chemotherapy　platinum-based　drugs.　This　study　provides　novel　insights　into　exploring　new　forms　of　metal　cluster-based　platinum　drugs　with　high　efficiency　for　optimizing　therapeutic　efficacy　while　minimizing　systemic　toxicity.　©　2024　Elsevier　Ltd