Rationale:　Although　neoantigen-based　cancer　vaccines　have　shown　promise　in　various　solid　tumors,　limited　immune　responses　and　clinical　outcomes　have　been　reported　in　patients　with　advanced　disease.　Cytosolic　transport　of　neoantigen　and　adjuvant　is　required　for　the　activation　of　intracellular　Toll-like　receptors　(TLRs)　and　cross-presentation　to　prime　neoantigen-specific　CD8+T　cells　but　remains　a　significant　challenge.Methods:　In　this　study,　we　aimed　to　develop　a　virus-like　silicon　vaccine　(V-scVLPs)　with　a　unique　spike　topological　structure,　capable　of　efficiently　co-delivering　a　hepatocellular　carcinoma　(HCC)-specific　neoantigen　and　a　TLR9　agonist　to　dendritic　cells　(DCs)　to　induce　a　robust　CD8+T　cell　response　to　prevent　orthotopic　tumor　growth.　We　evaluated　the　antitumor　efficacy　of　V-scVLPs　by　examining　tumor　growth　and　survival　time　in　animal　models,　as　well　as　analyzing　tumor-infiltrating　CD8+T　cells　and　cytokine　responses　in　the　tumor　microenvironment　(TME).　To　evaluate　the　synergistic　efficacy　of　V-scVLPs　in　combination　with　&　alpha;-TIM-3　in　HCC,　we　used　an　orthotopic　HCC　mouse　model,　a　lung　metastasis　model,　and　a　tumor　rechallenge　model　after　hepatectomy.　Results:　We　found　that　V-scVLPs　can　efficiently　co-deliver　the　hepatocellular　carcinoma　(HCC)-specific　neoantigen　and　the　TLR9　agonist　to　DCs　via　caveolin-mediated　endocytosis.　This　advanced　delivery　strategy　results　in　efficient　lymph　node　draining　of　V-scVLPs　to　activate　lymphoid　DC　maturation　for　promoting　robust　CD8+T　cells　and　central　memory　T　cells　responses,　which　effectively　prevents　orthotopic　HCC　tumor　growth.　However,　in　the　established　orthotopic　liver　tumor　models,　the　inhibitory　receptor　of　TIM-3　was　significantly　upregulated　in　tumor-infiltrating　CD8+T　cells　after　immunization　with　V-scVLPs.　Blocking　the　TIM-3　signaling　further　restored　the　antitumor　activity　of　V-scVLPs-induced　CD8+T　cells,　reduced　the　proportion　of　regulatory　T　cells,　and　increased　the　levels　of　cytokines　to　alter　the　tumor　microenvironment　to　efficiently　suppress　established　orthotopic　HCC　tumor　growth,　and　inhibit　lung　metastasis　as　well　as　recurrence　after　hepatectomy.Conclusion:　Overall,　the　developed　novel　spike　nanoparticles　with　efficient　neoantigen　and　adjuvant　intracellular　delivery　capability　holds　great　promise　for　future　clinical　translation　to　improve　HCC　immunotherapy.