Rubropunctatin　is　a　natural　and　harmless　secondary　metabolite　of　the　fungus　Monascus　with　promising　anticancer　properties.　However,　its　water　insolubility　affects　its　distribution　and　absorption　in　vivo,　its　bioavailability　and　further　application　in　the　clinic　is　limited.　Herein,　a　core-shell　nano-micelle　Rubropunctatin　Deoxycholate　Sodium/Poloxamer　188/Phospholipid　nano-micelle　(RDPP-MNPs)　was　prepared　by　the　film　evaporation.　RDPP-MNPs　exhibited　uniform　size　(152.73　f　1.55　nm),　low　CMC　(0.027　f　0.010　mg/mL)　and　pHsensitive　sustained　release,　which　effectively　prolonged　the　circulation　time　of　the　drugs　in　vivo.　The　results　of　CCK-8　cytotoxicity　experiment　showed　that　RDPP-MNPs　could　significantly　inhibit　the　activity　of　Hela　and　4T1　cells　(IC50　=　7.73　f　0.09　mu　g/mL,　IC50　=　9.25　f　0.19　mu　g/mL),　respectively.　In　addition,　RDPP-MNPs　have　a　greater　ability　to　induce　apoptosis　of　Hela　cells　by　promoting　the　uptake　of　drugs　into　cells　in　a　concentrationdependent　manner.　Finally,　we　verified　the　tumor　inhibitory　effect　and　biosafety　of　RDPP-MNPs　by　tumorbearing　mouse　model.　The　tumor　inhibition　rate　was　up　to　71.49　f　3.53　%　with　no　systemic　toxicity,　validated　by　organ　histology.　These　results　showed　that　the　therapeutic　efficacy　of　Rubropunctatin　could　be　significantly　enhanced　by　DPP-MNPs.　And　based　on　its　good　anti-cancer　activity,　bioavailability　and　biosafety,　it　has　potential　in　gentle　chemotherapy　and　can　reference　other　natural　compounds　in　cancer　therapy.