This dataset contains TMT-based quantitative proteomic profiles of fluorescence-activated cell sorting–isolated normoxic and hypoxic neuroblastoma cells collected from normoxic–hypoxic co-culture experiments. Three independent biological replicates were analyzed per condition. Proteins were extracted, digested with Lys-C and trypsin, labeled with TMT reagents, pooled, and fractionated by basic reversed-phase chromatography using C18 StageTips. LC–MS/MS analysis was performed using an Orbitrap Fusion Lumos mass spectrometer. The dataset was generated to characterize proteomic alterations associated with intercellular interactions and the adaptive response of hypoxic neuroblastoma cells during co-culture.