MicroRNA-34a　(miR-34a)　modulation　therapy　has　shown　great　promise　to　treat　hepatocellular　carcinoma　(HCC).　2＇-Hydroxy-2,4,4＇,5,6＇-pentamethoxychalcone,　termed　Rubone,　has　been　shown　to　specifically　upregulate　miR-34a　expression　in　HCC　cells　and　considered　as　novel　anticancer　agent.　However,　the　extremely　low　aqueous　solubility　of　Rubone　hampers　its　use　in　cancer　treatment.　In　the　present　study,　surface-stabilized　nanoparticles-based　delivery　strategy　was　engaged　to　overcome　this　impediment.　In　our　preparation,　Rubone　was　encapsulated　in　the　micelles　composed　of　polyethylenimine-poly(epsilon-caprolactone)　(PEI-PCL)　through　hydrophobic　interactions,　which　were　subsequently　stabilized　with　anionic　carboxymethyl　dextran　CMD　via　electronic　interaction.　We　found　that　Rubone-encapsulating　nanoparticles　are　dispersed　well　in　aqueous　solution.　The　results　further　demonstrated　that　Rubone　could　be　efficiently　delivered　in　HCC　cells　by　nanoparticles　and　upregulate　miR-34a　expression,　which　in　turn　led　to　inhibition　of　proliferation,　migration,　and　increased　apoptosis　of　HCC　cells.　In　vivo　experiments　showed　that　Rubone　can　be　preferentially　delivered　into　tumor　tissues　by　CMD-stabilized　PEI-PCL　nanoparticles　after　intravenous　administration　and　significantly　inhibited　tumor　growth.　Furthermore,　low　cytotoxicity　of　the　nanoparticles　was　observed　in　vitro　and　in　vivo　analyses,　indicating　a　good　compatibility　of　generated　nanoparticles.　The　obtained　results　suggest　that　CMD-stabilized　PEI-PCL　nanoparticles　may　serve　as　a　novel　approach　for　small-molecule-modulator　mediated　miR-34a　restoration　for　HCC　therapy.