Introduction <p>Neuroblastoma (NB) is the most common extracranial solid tumour in children, with low 5-year survival rates in high-risk cases. Identifying new tumour biomarkers is essential for risk stratification. This study investigated the potential of LC3B as a prognostic biomarker for high-risk NB.</p> Methods <p>Peripheral blood, tissue samples, and clinical data were collected from 53 children with NB. The expression rates of 16 biomarker antibodies in peripheral blood mononuclear cells were analysed using flow cytometry. NB mRNA expression profiles and clinical data from 282 tissue samples were obtained from the Gene Expression Omnibus database (GSE49710). Multivariate logistic regression assessed factors influencing high-risk NB, and a receiver operating characteristic curve (ROC) was plotted.</p> Results <p>Flow cytometry revealed that LC3B expression in peripheral blood mononuclear cells was significantly lower in the high-risk group compared to the low-intermediate-risk groups (<i>P</i> &lt; 0.05). Analysis of the Gene Expression Omnibus database indicated that LC3B mRNA was highly expressed in low- to intermediate-risk patients but weakly in high-risk patients (<i>P</i> &lt; 0.01). ROC analysis showed that LC3B expression has prognostic value for high-risk NB [AUC = 0.684, 95% CI: (0.541, 0.827)], which improves when combined with neuron-specific enolase (NSE) [AUC = 0.789, 95% CI: (0.667, 0.911)]. The expression level of LC3B mRNA in tumour tissues provided the best prognostic model for high-risk NB [AUC = 0.855, 95% CI: (0.808, 0.903)].</p> Conclusion <p>LC3B may be a novel prognostic biomarker for screening high-risk patients with NB, and combined detection with NSE could enhance prognostic accuracy.</p>