Neuroblastoma is a solid tumour of the developing sympathetic nervous system that occurs during childhood, usually diagnosed in children younger than 5 years old. Genomic investigations into neuroblastoma have uncovered few recurrent actionable mutations for targeted therapy, and amplification of the MYCN oncogene remains the single most important genetic predictor of poor prognosis. However, the protein structure of MYCN is extremely difficult to target, as it has few suitable docking sites for small molecule inhibitors. Therefore, identification of co-factors that interact with MYCN is an alternative approach to indirectly target MYCN. A proteomics screen was conducted to identify novel candidate MYCN binding proteins using a stable cell line with MYCN overexpression. Interestingly, candidate binding partners that have been identified through this screen include splicing associated proteins hnRNP F and SNRPD3, suggesting a potential functional dependence for MYCN in the regulation of alternative splicing. In this study, we aimed to determine the potential oncogenic function of hnRNP F and SNRPD3 in neuroblastoma and assess their relevance to MYCN activity. Using phenotypic assays, we observed that the knockdown of SNRPD3 reduces cell viability and proliferation in MYCN-amplified neuroblastoma cell lines. Further investigation using an inducible MYCN system revealed that the reduction of cell viability through the knockdown of SNRPD3 is MYCN-dependant. Furthermore, the inducible knockdown of MYCN by the addition of doxycycline reduced hnRNP F and SNRPD3 protein and mRNA expression. Multivariate analysis of high hnRNP F and SNRPD3 expression in a 649 neuroblastoma patients cohort revealed that both hnRNP F and SNRPD3 are independent indicators of poor prognosis. Based on these results, we suggest that MYCN-driven transcriptional up-regulation and physical interaction with hnRNP F and SNRPD3 contributes to changes in alternative splicing that perpetuate MYCN-driven oncogenesis. The synthetic lethal relationship exhibited between MYCN and SNRPD3 indicates that SNRPD3 could serve as a novel therapeutic target in MYCN-amplified neuroblastoma.