In　this　study,　we　construct　a　multiple　amplification　biosensor　combining　a　hybridization–digestion　cycles　in　a　homogeneous　reaction　in　liquid　phase,　and　a　modified　streptavidin-biotin　complex　(SABC)　method.　To　reduce　the　number　of　DNA　types　participating　in　the　hybridization–digestion　cycles,　we　design　a　dual-functional　reporter　probe　with　biotin　and　-PO4　in　both　distal　ends,　which　can　not　only　hybridize　with　the　target　DNA　and　be　recognized　by　λ-exo　but　also　bind　to　streptavidin.　The　target　DNA　hybridized　with　the　reporter　probe,　and　then　the　reporter　sequence　was　digested　by　λ-exo　to　release　the　target　DNA.　After　the　hybridization–digestion　cycles,　the　remaining　reporter　probe　was　captured　by　the　probe　mobilized　on　the　gold　electrode.　Meanwhile,　in　modified　SABC　method,　we　mixed　streptavidin-horseradish　peroxidase　(SA-HRP)　and　biotin-HRP　to　form　complexes,　which　bind　to　biotin　on　reporter　probe　to　accumulate　large　amounts　of　HRP　on　the　electrode,　current　was　further　increased　on　the　basis　of　the　HRP-catalyzed　reaction.　By　the　combination　of　this　two　signal　amplification　protocols,　the　detection　limit　of　this　biosensor　was　1　pM.　Wild-type　EGFR　in　clinical　samples　from　lung　cancer　patients　can　be　successfully　discriminated　from　EGFR　mutations　by　the　proposed　method.　Our　research　would　make　the　electrochemical　biosensor　be　an　excellent　candidate　for　EGFR　status　detection　in　clinical　diagnosis　and　prognosis.　©　2019　Elsevier　B.V.