We　developed　a　circular　bivalent　aptamer　(CBA)　to　precisely　activate　membrane　receptor-mediated　regenerative　signaling　for　liver　repair　in　vivo.　The　CBA　showed　enhanced　biostability　and　receptor　binding　avidity,　achieving　effective　pathway　activation　and　satisfactory　treatment　in　an　acetaminophen-induced　liver　injury　model.　This　work　expands　aptamer-based　molecular　engineering　in　regenerative　medicine.