Neuroblastoma (NB) is the most common solid tumor in childhood. Twenty percent of patients display amplification, which indicates a very poor prognosis. is a highly specific target for an NB tumor therapy as expression is absent or very low in most normal cells, while, as a transcription factor, it regulates many essential cell activities in tumor cells. We aim to develop a therapy for NB based on silencing by short interfering RNA (siRNA) molecules, which can silence target genes by RNA interference (RNAi), a naturally occurring method of gene silencing. It has been shown previously that silencing can induce apoptosis and differentiation in amplified NB. In this article, we have demonstrated that siRNA-mediated silencing of in -amplified NB cells induced neurogenesis in NB cells, whereas retinoic acid (RA) treatment did not. RA can differentiate NB cells and is used for treatment of residual disease after surgery or chemotherapy, but resistance can develop. In addition, siRNA treatment suppressed growth in a -amplified NB cell line more than that by RA. Our result suggests that gene therapy using RNAi targeting can be a novel therapy toward -amplified NB that have complete or partial resistance toward RA.