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Resveratrol, polyphenol naturally occurring in grapes or nuts, has anti-cancer properties in the treatment of neuroblastoma – the most common childhood solid tumor. It affects cancer cells by increasing apoptosis, inducing cell necrosis and reducing tumor mass. Mechanism of action – (1) converting procaspases, mainly procaspases three and nine into active forms – caspases, (2) blocking kinases, and also (3) leading the cell to the S-cell cycle, where it is most effective while increasing the concentration of cyclin E and lowering the concentration of p21 protein. In vitro, as well as, rodent animal models studies are available and show promising results. Therapeutic doses, currently within 10–100 μmol/L, are also being tested, as well as other forms of resveratrol, such as its trans-4,4′-dihydroxystilbene analog and polyphenol lipoconjugates. In our review, we presented the known molecular mechanisms of polyphenol anti-tumor activity against neuroblastoma and discussed the studies confirming its effectiveness.