Abstract Background The rs2147578 C > G polymorphism in the long non-coding RNA gene Lnc-LAMC2–1:1 is associated with increased susceptibility to a few types of cancers. However, its role in neuroblastoma has not been evaluated yet. Methods We investigated the association between the lnc-LAMC2–1:1 rs2147578 C > G polymorphism and neuroblastoma susceptibility in Chinese Han populations. A total of 393 neuroblastoma cases and 812 healthy individuals from the Henan and Guangdong provinces were enrolled and subjected to genotyping. Odds ratio (OR) and 95% confidence interval (CI) were used to determine the strength of the association of interest. Results Combined analysis revealed that the lnc-LAMC2–1:1 rs2147578 C > G polymorphism was associated with increased neuroblastoma susceptibility (CG vs. CC: adjusted OR = 1.33, 95% CI = 1.01–1.75, P = 0.045; CG/GG vs. CC: adjusted OR = 1.34, 95% CI = 1.03–1.74, P = 0.028). In stratification analysis, children under 18 months with rs2147578 CG/GG genotypes had an increased neuroblastoma risk (adjusted OR = 1.70, 95% CI = 1.08–2.67, P = 0.022). Females with rs2147578 CG/GG genotypes also had increased neuroblastoma susceptibility (adjusted OR = 2.08, 95% CI = 1.37–3.18, P = 0.0007). In addition, children with lnc-LAMC2–1:1 rs2147578 CG/GG genotypes were prone to develop earlier stages of neuroblastoma (adjusted OR = 1.46, 95% CI = 1.01–2.12, P = 0.046). Conclusions The Lnc-LAMC2–1:1 rs2147578 C > G polymorphism may contribute to increased neuroblastoma susceptibility in children of Henan province.