The current study demonstrates that SIRT1 functions as an oncoprotein in N-Myc oncogenesis through forming a transcriptional repressor complex with N-Myc, repressing MKP3 gene transcription and consequently stabilizing N-Myc oncoprotein, and that SIRT1 inhibitors exert anticancer effects against N-Myc-induced neuroblastoma in vitro and in vivo. Here, MYCN is linked to neuroblastoma.