mRNA　vaccines　are　regarded　as　a　highly　promising　avenue　for　next-generation　cancer　therapy.　Nevertheless,　the　intricacy　of　production,　inherent　instability,　and　low　expression　persistence　of　linear　mRNA　significantly　restrict　their　extensive　utilization.　Circular　RNAs　(circRNAs)　offer　a　novel　solution　to　these　limitations　due　to　their　efficient　protein　expression　ability,　which　can　be　rapidly　generated　in　vitro　without　the　need　for　extra　modifications.　Here,　we　present　a　novel　neoantigen　vaccine　based　on　circRNA　that　induces　a　potent　anti-tumor　immune　response　by　expressing　hepatocellular　carcinoma-specific　tumor　neoantigens.　By　cyclizing　linearRNA　molecules,　we　were　able　to　enhance　the　stability　of　RNA　vaccines　and　form　highly　stable　circRNA　molecules　with　the　capacity　for　sustained　protein　expression.　We　confirmed　that　neoantigen-encoded　circRNA　can　promote　dendritic　cell　(DC)　activation　and　enhance　DC-induced　T-cell　activation　in　vitro,　thereby　enhancing　T-cell　killing　of　tumor　cells.　Encapsulating　neoantigen-encoded　circRNA　within　lipid　nanoparticles　for　in　vivo　expression　has　enabled　the　creation　of　a　novel　circRNA　vaccine　platform.　This　platform　demonstrates　superior　tumor　treatment　and　prevention　in　various　murine　tumor　models,　eliciting　a　robust　T-cell　immune　response.　Our　circRNA　neoantigen　vaccine　offers　new　options　and　application　prospects　for　neoantigen　immunotherapy　in　solid　tumors.　This　study　developed　a　novel　circRNA-based　neoantigen　vaccine.　In　vitro　experiments　showed　that　circRNA　encoding　neoantigens　can　promote　DC　activation　and　enhance　DC-induced　T-cell　activation　in　vitro,　thereby　enhancing　T-cell　killing　of　tumor　cells.　The　circRNA　neoantigen　vaccine　exhibited　potent　therapeutic　and　prophylactic　effects　in　diverse　murine　tumor　models　by　eliciting　a　robust　T-cell-mediated　immune　response.　image