We found that: (1) lncRNA NHEG1 was upregulated in NB and correlated with prognosis of NB patients; (2) downregulation of lncRNA NHEG1 could inhibit the proliferation, migration, and invasion of NB cells; (3) the miR-665/HMGB1 axis, which was also previously reported to regulate retinoblastoma [24,25], may serve as the downstream effectors mediating the role of lncRNA NHEG1 in NB. The gene discussed is HMGB1; the disease is neuroblastoma.