Baicalin　(BAI)　has　been　reported　to　exert　antitumor　effects.　However,　BAI　has　limited　water　solubility,　non-specific　tumor　targeting,　and　low　bioavailability,　which　severely　limited　its　clinical　application.　The　aim　of　this　study　was　to　develop　folic　acid　(FA)　covalently　conjugated-polyamidoamine　(PAMAM)　dendrimers　(PAMAM-FA)　as　carrier　systems　for　improvement　of　water　solubility　and　tumor-specificity　of　BAI,　and　study　the　role　of　generation　on　the　physiochemical　properties　and　biological　effects　of　PAMAM-FA/BAI　complexes.　In　this　work,　four　generations　of　PAMAM-FA　were　synthesized　to　entrap　BAI.　The　average　sizes　of　G3-FA/BAI,　G4-FA/BAI,　G5-FA/BAI,　and　G6-FA/BAI　complexes　were　174.4 nm,　184.5 nm,　258.8 nm,　and　247.5 nm,　respectively,　and　the　zeta　potentials　of　four　PAMAM-FA/BAI　complexes　were　− 2.9 mV,　− 6.6 mV,　− 9.3 mV,　− 9.0 mV,　respectively.　The　entrapment　efficiencies　of　four　PAMAM-FA/BAI　complexes　were　91.1%,　53.5%,　80.3%,　and　91.9%,　respectively,　and　the　drug　loading　of　PAMAM-FA/BAI　complexes　were　about　22%.　The　formed　PAMAM-FA/BAI　complexes　allowed　sustained　release　of　BAI　in　acidic　PBS　(pH 5.4).　In　cellular　uptake　assay,　PAMAM-FA/BAI　complexes　demonstrated　increased　drug　uptake　level　in　folate　receptor　(FR)-positive　Hela　cancer　cells　than　FR-negative　A549　cells,　and　the　cellular　uptake　efficiency　of　PAMAM-FA　is　closely　related　with　the　generation　of　PAMAM.　The　MTT　assay　results　showed　that　PAMAM-FA/BAI　complexes　demonstrated　enhanced　toxicity　against　Hela　cells　than　non-FA-modified　PAMAM/BAI　complexes,　and　the　G6-FA/BAI　demonstrated　the　best　inhibition　efficiency.　The　cell　cycle　and　cell　apoptosis　analysis　further　demonstrated　the　tumor-specific　therapeutic　efficacy　of　PAMAM-FA/BAI.　These　results　suggested　that　the　PAMAM-FA　have　the　potential　for　targeted　delivery　of　BAI　into　cancer　cells　to　enhance　its　anti-tumor　efficacy.　©　2017　Elsevier　B.V.