In this study, we attempted to investigate in what measure p300, FOXO3, and Sirt1 might affect the development of IDD via regulation of the Wnt/β‐catenin pathway; our results showed that p300‐mediated FOXO3 increases in Sirt1 inhibited the Wnt/β‐catenin pathway, which promotes autophagy and inhibits apoptosis of NPCs. Here, SIRT1 is linked to intervertebral disk degenerative disorder.