Ischemic stroke is an acute cerebrovascular disease caused by cerebral vascular obstruction, which is the third leading cause of human death and disability. Multiple studies have demonstrated that autophagy plays a positive role in neurons after ischemic stroke. Autophagy is the main intracellular mechanism that mediates the degradation and recycling of various substrates in lysosomes, so it is very important to maintain normal function of lysosomes. However, cerebral ischemia can result in significant impairment of lysosomal function, subsequently leading to disruption in autophagy flow and exacerbation of neuronal injury. This review elucidates the mechanism of autophagic flux injury resulting from lysosomal dysfunction induced by impaired fusion between autophagosomes and lysosomes, alterations in the acidic environment within lysosomes, and diminished biosynthesis of lysosomes following ischemic stroke. The lysosome is regarded as the primary focal point for investigating the mechanism of autophagic flux injury, with the aim of modulating neuronal autophagic flux to improve cerebral ischemia-induced brain injury. This approach holds potential for exerting a neuroprotective effect and providing a novel avenue for stroke treatment.