Purpose:　Combination　therapy　for　tumors　is　an　important　and　promising　strategy　to　improve　therapeutic　efficiency.　This　study　aims　at　combining　tumor　targeting,　chemo-,　and　photodynamic　therapies　to　improve　the　anti-tumor　performance.　Patients　and　Methods:　Human　serum　albumin　(HSA),　as　a　nontoxic　and　biodegradable　drug　carrier,　was　used　to　load　hydrophobic　photosensitizers　(mono-substituted　β-4-pyridy-loxy　phthalocyanine　zinc,　mPPZ)　by　a　dilution-incubation-purification　(DIP)　strategy　to　form　molecular　complex　HSA:mPPZ.　This　complex　was　cross-linked　as　nanoparticles,　and　then　chemotherapy　drug　doxorubicin　(DOX)　was　adsorbed　into　the　nanoparticles　to　achieve　combined　photodynamic　therapy　and　chemotherapy.　Next,　the　surface　of　the　obtained　composite　was　modified　by　a　tumor　surface　receptor　(urokinase　receptor)　targeting　agent　(ATF-HSA)　using　a　noncovalent　method　to　obtain　the　final　product　(ATF-HSA@HSA:　mPPZ:DOX　nanoparticles,　AHmDN).　Results:　AHmDN　exhibited　strong　stability,　remarkable　cytotoxicity　and　higher　uptake　to　tumor　cells.　Cell　imaging　analysis　indicated　that　DOX　was　separated　from　AHmDN　and　uniformly　distributed　in　cell　nucleus　while　mPPZ　localized　in　cytoplasm.　The　PDT　activity　of　all　the　samples　had　been　confirmed　by　the　detection　of　intracellular　ROS.　In　animal　experiments,　AHmDN　was　demonstrated　to　have　a　prominent　tumor-targeting　effect　using　a　3D　imaging　system.　In　addition,　the　enhanced　antitumor　effect　of　AHmDN　in　tumor-bearing　mice　was　also　been　observed.　Importantly,　the　tumor-targeting　effect　of　such　nanoparticles　lasted　for　about　14　days　after　one　injection.　Conclusion:　These　albumin　nanoparticles　with　combined　functions　of　tumor　targeting,　chemotherapy　and　photodynamic　therapy　can　highly　enhance　the　anti-tumor　effect.　This　drug　delivery　system　can　be　applied　to　package　other　hydrophobic　photosensitizers　and　chemotherapy　drugs　for　improving　therapeutic　efficacy　to　tumors.　©　2020　Zheng　et　al.