Neuroblastoma (NB) is the most common extracranial, solid paediatric tumour, and the molecular mechanisms responsible for the pathogenesis of NB remain elusive. In our previous studies, we found that SOX2 was highly expressed in NB tissues, and its expression correlated with the NB clinical stage. We further found that in I-type neuroblastoma cells (BE (2)-C cells) while SOX2 mRNA expression was knocked down by gene-specific siRNA (small interference RNA), the tumourigenicity of the cells was significantly decreased, but the cells had increased expression levels of marker proteins of N- or S-type cells. The objective of this study was to investigate the effect of SOX2 siRNA on the gene expression profiles of neuroblastoma BE (2)-C cells. According to the results of the gene expression study, 1744 differentially expressed genes (DEGs) were discovered; 596 DEGs related to SOX2 siRNA were determined by cluster analysis. Ten Gene Ontology (GO) functional categories with the smallest P-values in the upregulated and downregulated clusters were determined by GO analysis. Some crucial signalling pathways (Wnt, MAPK, ErbB, etc.) are known to be affected by these genes. These results demonstrate that SOX2 regulates several significant genes, which in turn activate important pathways such as the Wnt signalling pathway, ultimately playing a key role in the pathogenesis and progression of NB.