Background　Autophagy　is　closely　associated　with　apoptosis　in　H9c2　cardiomyocytes　as　a　result　of　hypoxia.　The　present　study　aimed　to　determine　whether　microRNAs　(miRs)　mediated　apoptosis　and　autophagy　in　hypoxia-stimulated　H9c2　cardiomyocytes.　Methods　miR　microarrays　and　quantitative　reverse　transcription-polymerase　chain　reaction　(qRT-PCR)　assays　were　used　to　detect　differentially　expressed　miRs　in　H9c2　cardiomyocytes　following　hypoxia　stimulation.　Annexin　V-fluorescein　isothiocyanate　double　staining　was　performed　to　evaluate　hypoxia-induced　cell　apoptosis,　and　the　protein　expression　levels　of　autophagy-associated　genes　were　detected　using　western　blotting.　Results　miR　microarrays　and　qRT-PCR　assays　showed　that　the　expression　of　miR-129-5p　is　significantly　decreased　in　hypoxia-exposed　H9c2　cardiomyocytes.　Under　hypoxic　stimulation,　miR-129-5p　mimics　alleviated　hypoxia-induced　cell　apoptosis　and　also　restored　autophagy　in　H9c2　cardiomyocytes.　However,　transfection　with　miR-129-5p　inhibitors　accelerated　hypoxia-induced　cell　apoptosis　and　autophagy　deficiency　in　H9c2　cardiomyocytes.　Furthermore,　overexpression　of　miR-129-5p　enhanced　cell　viability　and　reduced　the　release　of　lactate　dehydrogenase　in　hypoxia-stimulated　H9c2　cardiomyocytes.　Conclusions　These　findings　highlight　the　protective　effect　of　miR-129-5p　against　hypoxia-induced　apoptosis　in　H9c2　cardiomyocytes　through　the　activation　of　autophagy.