BackgroundNeuroblastoma is a common malignant tumor stemming from the sympathetic nervous system in children, which is often life‐threatening. The genetics of neuroblastoma remains unclear. Studies have shown that miRNAs participate in the regulation of a broad spectrum of biological pathways. The abnormity in the miRNA is associated with the risk of various cancers, including neuroblastoma. However, research on the relationship of miRNA polymorphisms with neuroblastoma susceptibility is still in the initial stage.MethodsIn this research, a retrospective case–control study was conducted to explore whether miR‐100 rs1834306 A > G polymorphism is associated with neuroblastoma susceptibility. We enrolled 402 cases and 473 controls for the study. The logistic regression analysis was adopted to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between miR‐100 rs1834306 A > G and neuroblastoma risk.ResultsOur results elucidated that the miR‐100 rs1834306 A > G polymorphism was associated with the decreased risk of neuroblastoma (AG versus AA: adjusted OR = 0.72, 95% CI = 0.53–0.98, and P = 0.038). The subsequent stratified analysis further found that rs1834306 AG/GG genotype reduced the risk of neuroblastoma in the subgroup with tumors of the mediastinum origin (adjusted OR = 0.63, 95% CI = 0.41–0.95, and P = 0.029).ConclusionsIn summary, miR‐100 rs1834306 A > G polymorphism was shown to associate with decreased neuroblastoma risk in Chinese children, especially for neuroblastoma of mediastinum origin. This conclusion needs to be verified in additional large‐size case–control studies.