Doxorubicin　(DOX)　is　an　effective　chemotherapy　drug　used　to　treat　different　types　of　cancers.　However,　DOX　has　severe　side　effects,　especially　life-threatening　cardiotoxicity.　We　herein　report　a　new　approach　to　reduce　the　toxicity　of　DOX　by　embedding　DOX　inside　human　serum　albumin　(HSA).　HSA　is　further　fused　by　a　molecular　biology　technique　with　a　tumor-targeting　agent,　amino-terminal　fragment　of　urokinase　(ATF).　ATF　binds　with　a　high　affinity　to　urokinase　receptor,　which　is　a　cell-surface　receptor　overexpressed　in　many　types　of　tumors.　The　as-prepared　macromolecule　complex　(ATF-HSA:DOX)　was　not　as　cytotoxic　as　free　DOX　to　cells　in　vitro,　and　was　mainly　localized　in　cell　cytosol　in　contrast　to　DOX　that　was　localized　in　cell　nuclei.　However,　in　tumor-bearing　mice,　ATF-HSA:DOX　was　demonstrated　to　have　an　enhanced　tumor-targeting　and　antitumor　efficacy　compared　with　free　DOX.　More　importantly,　histopathological　examinations　of　the　hearts　from　the　mice　treated　with　ATF-HSA:DOX　showed　a　significantly　reduced　cardiotoxicity　compared　with　hearts　from　mice　treated　with　free　DOX.　These　results　demonstrate　the　feasibility　of　this　approach　in　reducing　the　cardiotoxicity　of　DOX　while　strengthening　its　antitumor　efficacy.　Such　a　tumor-targeted　albumin　packaging　strategy　can　also　be　applied　to　other　antitumor　drugs.