Background:　Many　diseases　include　microRNAs　(miRNAs)　as　reported　biomarkers.　The　significance　of　circulating　miRNAs　for　early　diagnosis　of　acute　stroke　in　humans　is　unknown.　We　aim　to　determine　whether　circulating　miRNAs　potentially　serve　as　novel　biomarkers　for　acute　stroke.　Methods:　We　prospectively　recruited　patients　with　acute　stroke　and　those　with　nonstroke　disease.　Patients　with　acute　stroke　were　identified　using　magnetic　resonance　imaging　(MRI)　for　early　diagnosis.　If　the　patient　suffered　from　acute　stroke　that　was　detected　with　diffusion-weighted　imaging,　the　patient　was　defined　as　an　MRI(+)　patient.　Otherwise,　it　was　defined　as　an　MRI(-)　patient.　Circulating　miRNAs　were　measured　by　miRNA　microarray　and　real-time　polymerase　chain　reaction　(PCR)　analysis.　Results:　A　total　of　136　patients　were　included　in　the　study.　Testing　by　miRNA　microarray　and　real-time　PCR　analyses　showed　that　hsa-miR-106b-5P　and　hsa-miR-4306　were　present　with　markedly　high　abundance　in　patients　of　acute　stroke,　whereas　hsa-miR-320e　and　hsa-miR320d　were　present　with　quite　low　abundance　in　patients　compared　with　healthy　individuals.　Compared　with　healthy　individuals,　the　miRNAs　were　increased　as　in　patients　with　acute　stroke　as　follows:　hsa-miR-106b-5P,　3.63-fold　in　MRI(-)　patients　and　23.90-fold　in　MRI(+)　patients;　hsa-miR-4306,　3.19-fold　in　MRI(-)　patients　and　5.30-fold　in　MRI(+)　patients;　hsa-miR-320e,　.33-fold　in　MRI(-)　patients　and　.13-fold　in　MRI(+)　patients;　and　hsa-miR-320d,　.23-fold　in　MRI(-)　patients　and　.07-fold　in　MRI(+)　patients.　Conclusions:　Elevated　hsa-miR-106b-5P　and　hsa-miR4306　and　decreased　hsa-miR-320e　and　hsa-miR-320d　in　plasma　may　be　novel　biomarkers　for　the　early　detection　of　acute　stroke　in　humans.