Neuroblastoma (NB) is the most common solid extracranial tumor in children. However, the molecular mechanism of NB remains to be elucidated. In the present study, reverse transcription quantitative polymerase chain reaction data demonstrated that the expression of Sam68 was significantly upregulated in NB tissues compared with their matched adjacent normal tissues. Furthermore, it was revealed that reduced expression of miR‑203 and increased expression of Sam68 co‑existed in NB tissues. Knockdown of Sam68 reduced the proliferation, migration and invasion of human SK‑N‑SH and SH‑SY5Y NB cells. Similarly, overexpression of miR‑203 also inhibited the proliferation, migration and invasion of these two cell lines. It was further demonstrated that the protein expression level of Sam68 was negatively mediated by miR‑203 in the SK‑N‑SH and SH‑SY5Y NB cells. Additionally, data from a dual luciferase reporter assay confirmed that miR‑203 directly targeted Sam68 by binding to its 3'‑untranslated region. In conclusion, the present study suggested for the first time, to the best of our knowledge, that the aberrant downregulation of miR‑203 may contribute to the aberrant upregulation of Sam68 in NB and that miR‑203 has an inhibitory role in malignant progression of NB by targeting Sam68. The present study provided evidence to support miR-203/Sam68 as a novel diagnostic or therapeutic targets for NB.