Ursolic　acid　(UA)　as　a　nature　product　exhibits　good　anti-cancer　activity,　low　toxicity,　and　good　liver　protection　features.　However,　the　low-solubility　and　poor　bioavailability　restrict　its　further　clinical　application.　To　overcome　this　problem,　a　pH-sensitive　prodrug　delivery　system　(UA@MSN-UA)　that　incorporated　acid-sensitive　linkage　between　drug　and　silica-based　mesoporous　nanosphere　(MSN)　was　successfully　designed　and　synthesized.　The　physicochemical　properties　of　the　UA@MSN-UA　nanoparticles　were　investigated　for　shape,　particle　size,　zeta　potential,　nitrogen　adsorption-desorption　and　infrared　(IR)　spectroscopy.　The　nanoparticles　were　further　evaluated　for　in　vitro　cytotoxicity,　including　proliferation　inhibition,　cell　cycle　distribution　and　apoptotic　effects　against　human　hepatocellular　carcinoma　HepG2　cells.　The　TEM　image　showed　that　the　size　of　synthesized　MSN　nanoparticle　was　a　near-spherical　shape　with　~　100　nm　diameter.　In　vitro　cytotoxicity　testing　demonstrated　that　UA@MSN-UA　nanoparticles　prodrug　exhibited　higher　proliferation　inhibition,　cell　cycle　arrest　at　the　G2/M　phase　and　significantly　caused　the　early　and　late　apoptosis　in　HepG2　cells,　which　would　be　contributed　to　high　loading　capacity,　high　cellular　uptake　and　sustained　release　of　UA.　Overall,　the　UA-modified　MSN　prodrug　delivery　system　can　be　a　promising　drug　carrier　for　improving　the　bioavailability　of　UA,　and　further　enhance　its　anti-cancer　efficacy.　©　2016　Elsevier　B.V.