This study investigates the molecular effects of polystyrene nanoplastics (PS NPs) on human neural stem cells (hNS1). PS NPs, with an average size of 30 nm, were exposed to hNS1 cells at concentrations of 0.5, 2.5, and 10 μg/mL for 4 days. The results show that PS NPs induce oxidative stress, cellular stress, DNA damage, alterations in inflammatory response, and apoptosis, which could lead to tissue damage and neurodevelopmental diseases. Specifically, the expression of genes related to stress response (hsp27/hspB1, hsp90α, hsp70/hspA5), oxidative damage response (Cu/ZnSOD1, MnSOD2, cat), DNA repair (gadd45α, rad51, xrrc1), apoptotic response (Cas3a, Cas7, p53, Bcl2), and mitochondrial response (Cox5A) were analyzed. The findings suggest that PS NPs alter the cellular response to stress, induce DNA damage, and activate apoptosis, highlighting the potential neurotoxic effects of these nanoparticles.This study investigates the molecular effects of polystyrene nanoplastics (PS NPs) on human neural stem cells (hNS1). PS NPs, with an average size of 30 nm, were exposed to hNS1 cells at concentrations of 0.5, 2.5, and 10 μg/mL for 4 days. The results show that PS NPs induce oxidative stress, cellular stress, DNA damage, alterations in inflammatory response, and apoptosis, which could lead to tissue damage and neurodevelopmental diseases. Specifically, the expression of genes related to stress response (hsp27/hspB1, hsp90α, hsp70/hspA5), oxidative damage response (Cu/ZnSOD1, MnSOD2, cat), DNA repair (gadd45α, rad51, xrrc1), apoptotic response (Cas3a, Cas7, p53, Bcl2), and mitochondrial response (Cox5A) were analyzed. The findings suggest that PS NPs alter the cellular response to stress, induce DNA damage, and activate apoptosis, highlighting the potential neurotoxic effects of these nanoparticles.