Multifunctional　nanocarriers　with　a　simple　structure　and　biocompatibility　for　bioimaging,　potential　tumor　targeting,　and　precise　antitumor　ability　are　promising　in　cancer　therapy.　Bioactive　glass　is　an　important　biomaterial　and　has　been　used　in　clinical　bone　tissue　repair　due　to　the　high　biocompatibility　and　bioactivity.　Herein,　we　report　fetal　bovine　serum　(FBS)-decorated　europium-doped　bioactive　glass　nanoparticles　(EuBGN@FBS)　with　excellent　biosafety　and　enhanced　tumor　targeting　for　cancer　imaging　and　therapy.　EuBGN@FBS　showed　the　controlled　photoluminescent　properties　and　pH-responsive　anticancer　drug　release　behavior.　The　FBS　decoration　significantly　enhanced　the　dispersibility　in　physiological　medium　and　improved　hemocompatibility　and　cellular　uptake　of　EuBGN.　Relative　to　EuBGN,　EuBGN@FBS　could　also　efficiently　image　the　cancer　cell　and　show　significantly　enhanced　targeted　tumor　imaging　and　chemotherapy　in　vivo　while　retaining　negligible　side　effects.　The　simple　and　biocompatible　structure　with　efficient　tumor　targeting,　imaging,　and　therapy　makes　EuBGN@FBS　highly　promising　in　future　cancer　therapy.　©　2021　American　Chemical　Society.