Cell　surface　receptors　play　a　critical　role　in　modulating　intracellular　signal　transduction,　making　them　important　drug　targets.　However,　it　remains　challenging　to　develop　a　selective　and　efficient　strategy　for　regulating　receptor　function.　Herein,　we　develop　a　strategy,　called　bispecific　aptamer　induced　artificial　protein-pairing,　to　selectively　regulate　receptor　function.　In　this　strategy,　bispecific　aptamer　probes　act　as　molecular　mediators　to　bind　to　both　a　target　receptor　protein　and　a　paired　protein,　which　brings　the　two　proteins　into　close　proximity　on　the　living　cell　membrane.　Importantly,　the　paired　proteins　work　not　only　as　a　cancer　biomarker　for　enhancing　cell　selectivity　but　also　as　a　blocking　assistant　to　inhibit　target　receptor　function　via　strong　steric　hindrance　effect.　Compared　with　single-aptamer-mediated　regulation,　the　proposed　bispecific　aptamer　probes　afford　substantial　improvement　in　selective　and　efficient　regulation　of　receptor　function　and　downstream　signaling　pathways.　This　work　offers　a　versatile　methodology　to　design　molecular　mediators　that　can　modulate　receptor　function,　thereby　providing　a　new　way　for　developing　novel　therapeutic　drugs.