As　a　common　plasma　protein,　alpha-fetoprotein　(AFP)　is　widely　applied　as　the　tumor　biomarker　for　the　diagnosis　of　many　cancers.　To　develop　a　low　cost,　high　sensitive　and　high-throughput　method　for　the　determination　of　AFP　is　significant　for　the　disease　diagnosis.　In　this　work,　an　immunoassay　with　sandwich-type　structures　was　performed　on　a　paper-based　chip　for　the　analysis　of　AFP.　AFP　could　be　captured　by　the　primary　antibodies　which　were　immobilized　on　the　paper　by　chitosan.　On　the　secondary　antibodies,　the　modified　initiator　DNAs　could　trigger　the　hybridization　chain　reaction　to　amplify　the　fluorescence　signals　for　AFP.　A　laser-induced　fluorescence　detector　coupled　with　an　interface　was　applied　to　detect　the　targets　on　the　paper-based　chip.　Under　the　optimized　conditions,　the　detection　limit　for　AFP　was　1.0　pg/mL.　For　every　test,　the　sample　solution　consumption　only　was　10　μL.　Finally,　the　method　was　applied　to　determine　the　AFP　in　serum　of　normal　person　and　hepatopaths　with　hepatic　malignant　tumor,　chronic　hepatitis　B　and　other　suspected　liver　diseases.　The　AFP　could　be　found　from　all　of　the　samples　and　the　results　were　similar　to　that　obtained　by　chemiluminescence　immunoassay.　The　recoveries　for　AFP　ranged　from　93.8%　to　106%,　which　indicated　the　method　was　reliable.　The　method　based　on　paper　chip　had　great　potential　in　the　application　of　AFP　determination.　©　2020　Elsevier　B.V.