This project contains DIA LC‑MS/MS proteomic profiling of nucleus pulposus tissues from 16 human patients with intervertebral disc degeneration (IDD) (6 Pfirrmann grade II, 10 grade V) to identify molecular changes associated with IDD progression. A total of 2,215 unique proteins were detected, 941 proteins met the within‑group missing‑rate filter (<50%) as high‑confidence identifications, and 194 proteins were differentially expressed between grade V and grade II (96 upregulated, 98 downregulated; |ratio|>1.2, p<0.05). Results highlight metabolic–immune pathway dysregulation in advanced IDD and supported downstream functional validation.