intervertebral disc degeneration (idd) is the main pathogenesis of numerous cases of chronic neck and back pain, and has become the leading cause of spinal-related disability worldwide. Hyperoside is an active flavonoid glycoside that exhibits anti-inflammation, anti-oxidation and anti-apoptosis effects. The purpose of the present study was to investigate the effect of hyperoside on tumor necrosis factor (TnF)-α-induced idd progression in human nucleus pulposus cells (nPcs) and its potential mechanism. The activity and apoptosis of nPcs were detected by cell counting Kit-8 and flow cytometry analyses, respectively. The expression of interleukin (il)-6 and il-1β was detected with eliSa kits. Western blotting was used to detect the expression levels of proteins. The results showed that hyperoside effectively alleviated TnF-α-induced nPc apoptosis, and hyperoside treatment inhibited the upregulation of inducible nitric oxide synthase, cyclooxygenase-2, il-1β and il-6 in TnF-α-stimulated nPcs. Compared with the findings in the TNF-α group, the intervention of hyperoside attenuated the upregulated expression of aggrecan and collagen ii, and downregulated the expressions of matrix metalloproteinase (MMP) 3, MMP13 and a disintegrin and metalloproteinase with thrombospondin motifs 5. in addition, hyperoside upregulated sirtuin-1 (SirT1) and nuclear factor e2-related factor 2 (nrf2) protein expression, and inhibition of SirT1 or nrf2 signaling reversed the protective effect of hyperoside on TnF-α-induced nPcs. in summary, hyperoside ameliorated TnF-α-induced inflammation, extracellular matrix degradation, and endoplasmic reticulum stress-mediated apoptosis, which may be associated with the regulation of the SirT1/nF-κB and nrf2/antioxidant responsive element signaling pathways by hyperoside.