Combination　with　chemotherapeutic　drug　and　gene　therapy　has　been　proven　highly　effective　in　suppressing　tumor　progression.　Hence,　an　asialoglycoprotein　receptor　(ASGPR)-targeting　nanodrug　delivery　system　based　on　mesoporous　silica　(MSN)　nanocarrier　for　co-delivery　of　sorafenib　(SO)　and　vascular　endothelial　growth　factor　(VEGF)　targeted　siRNA　(siVEGF)　to　hepatocellular　carcinoma　(HCC)　was　successfully　designed　and　synthesized.　The　structure　of　nanoparticles　was　characterized　by　IR,　particle　size,　zeta　potential　and　N2　adsorption-desorption.　The　nanoparticles　were　further　evaluated　for　drug　release,　cellular　uptake,　transfection,　cell　cytotoxicity　and　cell　cycle　against　HepG2　and　Huh7　cells.　In　vitro　testing　demonstrated　that　MSN-LA　delivery　system　could　not　only　induce　S　cell　cycle　arrest,　enhance　the　cytotoxicity　and　improve　the　tumor　target　of　SO　and　siVEGF,　but　also　enhance　the　siVEGF　transfection　efficiency　in　ASGPR-overexpressing　Huh7　cells.　Overall,　the　MSN-LA　delivery　system　can　be　a　promising　drug　carrier　which　could　further　enhance　the　anti-cancer　efficacy　of　SO　and　siVEGF　via　the　active　targeting　property　of　LA.　©　2017