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Intervertebral disc degeneration (IVDD) is a main cause of degenerative disc disease, which results in substantial pain among patients. However, the mechanism of degeneration remains unclear. Thus far, basic research on human IVDD has focused on only a limited number of proteins and has not been conducted from a holistic perspective. In this study, we used tandem mass tag (TMT) labeling combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to perform differential proteomic analysis on fetal and geriatric lumbar disc nucleus pulposus tissue. These data indicate that differential proteomics analysis may be an important method for elucidation of the pathophysiological process and molecular biological mechanism of human IVDD from a holistic perspective. The findings in this study will aid in screening of new biomarkers for early diagnosis and targeted treatment of IVDD.