Hepatocellular　carcinoma　(HCC)　commonly　emerges　in　an　immunologically　＇cold＇　state,　thereafter　protects　it　away　from　cytolytic　attack　by　tumor-infiltrating　lymphocytes,　resulting　in　poor　response　to　immunotherapy.　Herein,　an　acidic/photo-sensitive　dendritic　cell　(DCs)-based　neoantigen　nano-vaccine　has　been　explored　to　convert　tumor　immune　＇cold＇　state　into　＇hot＇,　and　remodel　tumor-associated　neutrophils　to　potentiate　anticancer　immune　response　for　enhancing　immunotherapy　efficiency.　The　nano-vaccine　is　constructed　by　SiPCCl2-hybridized　mesoporous　silica　with　coordination　of　Fe(III)-captopril,　and　coating　with　exfoliated　membrane　of　matured　DCs　by　H22-specific　neoantigen　stimulation.　The　nano-vaccines　actively　target　H22　tumors　and　induce　immunological　cell　death　to　boost　tumor-associated　antigen　release　by　the　generation　of　excess　1O2　through　photodynamic　therapy,　which　act　as　in　situ　tumor　vaccination　to　strengthen　antitumor　T-cell　response　against　primary　H22　tumor　growth.　Interestingly,　the　nano-vaccines　are　also　home　to　lymph　nodes　to　directly　induce　the　activation　and　proliferation　of　neoantigen-specific　T　cells　to　suppress　the　primary/distal　tumor　growth.　Moreover,　the　acidic-triggered　captopril　release　in　tumor　microenvironment　can　polarize　the　protumoral　N2　phenotype　neutrophils　to　antitumor　N1　phenotype　for　improving　the　immune　effects　to　achieve　complete　tumor　regression　(83%)　in　H22-bearing　mice　and　prolong　the　survival　time.　This　work　provides　an　alternative　approach　for　developing　novel　HCC　immunotherapy　strategies.　©　2022　The　Authors.　Advanced　Science　published　by　Wiley-VCH　GmbH.