Golgi　protein　73　(GP73)　is　a　potential　hepatocellular　carcinoma　serum　marker　with　better　sensitivity　and　specificity.　In　this　study,　a　highly　sensitive　electrochemical　immunosensor　which　combines　the　highly　selective　proximity　ligation　assay　(PLA)　and　highly　efficient　enzyme-powered　recycling　amplification　has　been　developed　for　GP73　determination.　PLA　is　triggered　by　affinity　binding　of　two　labelled　antibody-DNA　(P1-RAb　and　P2-MAb)　to　target　protein,　resulting　in　increased　specificity.　The　formed　immunocomplex　hybrids　with　DNA2　to　realize　the　release　of　methylene　blue　labelled　mononucleotides　fragment　with　the　help　of　exonuclease　III,　which　acts　as　the　power　of　recycling　amplification.　The　fragment　can　diffuse　easily　to　the　nafion　modified　indium　tin　oxide　electrode　surface　and　a　strong　electrochemical　signal　can　be　detected.　Under　the　optimized　conditions,　the　enhanced　electrochemical　intensity　has　a　linear　relationship　with　the　concentration　of　GP73　in　the　range　of　0.3　pg　mL−1　to　6.0　ng　mL−1　with　the　detection　limit　of　0.10　pg　mL−1.　The　developed　immunosensor　has　been　applied　to　detect　the　GP73　in　the　clinical　serum　samples　with　satisfactory　results.　©　2018　Elsevier　B.V.