Neurotoxins are numerous groups of drugs that lead detrimental effects on the neuronal system and caused the cognitive and neurological impairments. Intracellular signaling and homeostasis can disturb by those toxins. Lysosomes are crucial organelles to digest waste disposal and supply the essential materials. It is still unknown to connection between lysosomal homeostasis and neurological dysfunction. Here, we investigated how to attenuate the neurodegeneration though managing lysosomal function. After treatment of hydroperoxide as known as one of the neurotoxins, N2A cell proliferation decreased. Some neurotoxin reported to influence the lysosomal ion influx or efflux. When treatment by drugs, we disrupted the lysosomal ion exchange that N2A cell viability is protected by hydroperoxide. For intracellular signaling, hydroperoxide increased AKT phosphorylation, it also decreased after lysosomal ion exchange regulation. Hydroperoxide increases p-raptor protein level that functions as important component of mTORC1 that associated a fundamental role in lysosome, but it did not effect total raptor protein level. After starvation, the cell viability increased when we added hydroperoxide. It also cause to increased AKT phosphorylation and p-raptor level, but decreased by lysosome regulation. LC3 as known as a specific marker to sensing autophagy accelerated the treatment of hydroperoxide, but it also disrupted by lysosomal ion exchange control. Thus, the regulation of lysosomal activity prevents the neurodegeneration and associated intracellular signaling pathways by hydroperoxide.