N-Myc oncoprotein is over-expressed due to MYCN oncogene amplification in neuroblastoma, and is stabilized by phosphorylated ERK protein. Long noncoding RNAs (lncRNAs) are emerging as critical regulators in cancer. Our RNA sequencing revealed that RP1X was one of the five lncRNA transcripts most dramatically differentially expressed between MYCN-amplified and non-amplified human neuroblastoma cell lines. RT-PCR confirmed that knocking-down N-Myc expression with siRNAs reduced RP1X expression in MYCN-amplified neuroblastoma cells. Knocking-down RP1X expression with siRNAs reduced ERK protein phosphorylation, N-Myc protein phosphorylation at S62 and N-Myc protein expression, but showed no effect on N-Myc mRNA expression. Alamar blue assays and Annexin-V staining showed that RP1X siRNAs considerably reduced neuroblastoma cell proliferation and survival. In addition, in human neuroblastoma tissue samples, high levels of RP1X expression correlated with poor patient prognosis. The study therefore identifies RP1X as a novel co-factor for N-Myc protein stabilization, neuroblastoma cell proliferation and survival, and as a novel target for neuroblastoma therapy.