Intervertebral disc degeneration (IDD) is a kind of disease associated with nucleus pulposus (NP) cell senescence. Previous studies have shown that the sirtuin family plays an extremely important role in the progress of cell aging. However, whether sirtuin2 (Sirt2) protects against IDD remains unknown. The aim of this study was to determine whether Sirt2 protected NP from degradation in IDD. The expression of Sirt2 in different degree of degenerate disc tissues was determined by reverse transcription-polymerase chain reaction. Interleukin 1 beta (IL-1 beta) was used to stimulate the degeneration of NP cells. Subsequently, lentivirus transfection was performed to increase Sirt2 expression in vitro. Meanwhile, the function of Sirt2 overexpression in the progress of NP cell degeneration was evaluated. Our study showed that the expression of Sirt2 markedly decreased in severe degenerated disc tissues. IL-1 beta significantly promoted the progress of IDD. Meanwhile, overexpression of Sirt2 could reverse the effects of IL-1 beta. The data also revealed that Sirt2 overexpression obviously increased the production of antioxidant SOD1/2 and suppressed oxidative stress in the disc. Moreover, p53 and p21 could be significantly suppressed by Sirt2 overexpression. These results suggested that Sirt2 prevented NP degradation via restraining oxidative stress and cell senescence through inhibition of the p53/p21 pathway. Furthermore, Sirt2 might become a novel target for IDD therapy in the future. (C) 2019 Published by Elsevier Inc.