T-lymphocytes　play　a　potent　role　in　cancer　immunotherapy;　while,　limited　tumor　infiltrating　lymphocytes　(TILs)　combined　with　severe　immunosuppression　always　significantly　hinder　their　antitumor　immune　responses,　especially　in　solid　tumors　such　as　hepatocellular　carcinoma　(HCC).　Here,　we　prepared　a　highly　stable　multifunctional　aptamer　for　strengthening　antitumor　immunity　against　HCC　solid　tumors　through　a　dual　immune　checkpoint　blockade　of　CTLA-4　and　PD-L1.　The　engineered　multifunctional　aptamer　(termed　P1/C4-bi-apt)　can　block　both　CTLA-4/B7　and　PD-1/PD-L1　signaling　pathways　and　thus　enhance　the　antitumor　immune　responses.　Furthermore,　it　can　direct　CTLA-4-positive　T　cells　to　infiltrate　into　tumors　to　further　enhance　the　antitumor　efficacy　compared　to　a　single　blockage　of　CTLA-4　or　PD-L1.　As　a　result,　the　multifunctional　aptamer　can　significantly　inhibit　tumor　growth　and　thus　improve　the　long-term　survival　of　HCC-bearing　mice.　The　designed　multifunctional　aptamer　is　simple,　stable　and　easy　to　prepare,　and　it　can　significantly　strengthen　the　functionality　of　T　cells,　holding　great　potential　for　HCC　immunotherapy.　©　2021　The　Royal　Society　of　Chemistry.