In prior studies, Quercetin was revealed to exhibit anticancer features in a variety of cancer cell lines.However, the impact of Quercetin on neuroblastoma is unknown. This study looked into the potential cytotoxic effects of Quercetin and Quercetin-loaded chitosan nanoparticles (NPs) on the SH-SY5Y cell line. In this study, NPs containing Quercetin was prepared and characterization studies were performed.The vitality of the cells was measured using the XTT test after 24 hours of treatment with various concentrations of Quercetin (0.5, 1, 2, 4, and 8 µg/mL). ELISA kits were used to detect the amounts of cleaved PARP, BCL-2, 8-Hydroxy-deoxyguanosine (8-oxo-dG), cleaved caspase 3, Bax, total oxidant, and total antioxidant in the cells. The results of the chitosan NPs characterization investigation revealed that the particle size, encapsulation effectiveness, and drug release pro le of NPs were all appropriate for cell culture studies. Quercetin and Quercetin-loaded chitosan NPs signi cantly reduced cell viability in SH-SY5Y cells at different concentrations (**p < 0.05). 2 µg/mL Quercetin and Quercetin-loaded chitosan NPs signi cantly enhanced the levels of 8-oxo-dG, cleaved caspase 3, Bax, cleaved PARP, and total oxidant in ELISA testing. However, treatment with 2 µg/mL of Quercetin and Quercetin-loaded chitosan NPs did not affect the amount of BCL-2 protein. Overall, Quercetin and Quercetin-loaded chitosan NPs caused signi cant cytotoxicity in SH-SY5Y cells via producing oxidative stress, DNA damage, and eventually apoptosis.