MYCN gene plays an important role in neuroblastoma cell growth, apoptosis, differentiation, tumor infiltration, metastasis, and angiogenesis. MYCN gene amplification status in tumor tissue is one of the important clinical indicators of neuroblastoma risk. However, there are several problems in detecting the MYCN gene in tumor tissues, such as complex procedures in detection approaches, high detection costs, and difficulty in obtaining tumor tissues. Studies have shown that circulating-free MYCN gene amplification in neuroblastoma is consistent with that in tumor tissue. Circulating-free MYCN gene amplification has the advantages of high sensitivity, high specificity, simple operation, and non-invasiveness as an indicator for prognosis and recurrence of neuroblastoma. Therefore, the application and future development of circulating-free MYCN gene amplification status in the prognosis and recurrence monitoring of neuroblastoma was examined in this article.