Co-delivery　multiple　drugs　using　nanocarriers　has　been　recognized　as　a　promising　strategy　for　cancer　treatment　to　enhance　therapeutic　efficacy.　In　this　study,　a　pH　sensitive　mesoporous　silica　nanoparticles　(MSN)　based　controlled　release　nanoparticles　for　co-delivery　of　sorafenib　(SO),　a　multi-tyrosine　kinase　inhibitor,　and　ursolic　acid　(UA),　a　sensitive　agent　for　SO,　was　developed,　which　was　decorated　with　pH　sensitive　chitosan　(CS)　and　lactobionic　acid　(LA)　targeting　to　asialoglycoprotein　receptor　(ASGPR)　over-expressing　hepatocellar　carcinoma　cells　(denoted　as　USMNs-CL).　The　nanocomplex　enhanced　bioavailability　of　hydrophobic　drugs,　efficient　tumor　cell　targeting　and　exhibited　pH-responsive　function　and　sustained　release　profile.　USMNs-CL　showed　synergistic　cytotoxicity　and　could　attenuate　the　adhesion,　migration　of　ASGPR　over-expressing　liver　cancer　SMMC-7721　cells　at　non-toxic　concentrations.　Moreover,　the　complex　nanoparticles　significantly　increased　the　cellular　apoptosis　and　down-regulated　the　expression　of　EGFR　and　VEGFR2　proteins　related　with　cell　proliferation　and　tumor　angiogenesis.　In　vivo,　compared　with　UA　or　SO　alone,　the　nanocomplex　significantly　reduced　the　tumor　burden　in　hepato-cellular　carcinoma　(HCC)　H22　tumor-bearing　mice　model　and　inhibited　the　lung　metastasis　in　the　H22　lung　metastasis　models.　Overall,　co-delivery　of　UA　and　SO　by　MSN-CS-IA　nanocarriers　could　provide　a　promising　strategy　for　HCC　combinational　therapy,　especially　for　the　HCC　metastasis　chemoprevention.　(C)　2017　Elsevier　Ltd.　All　rights　reserved.