miR-7c-5p was significantly decreased in the plasma of ischemic stroke patients and experimental animals.There was a significant decrease of let-7c-5p in the ipsilateral cortex and striatum of mice subjected to middle cerebral artery occlusion (MCAO) at 24 h reperfusion.Overexpression of let-7c-5p via ICV injection decreased the infarction volume and attenuated the neurological deficits.miR-7c-5p directly targeted the 30-untranslated region of the caspase 3 mRNA to reduce caspase 3 levels, which may underline the miRNA-modulated microglial activity. Here, CASP3 is linked to ischemic stroke.