[Objective]: To explore the effect of TNF-α on the senescence of nucleus pulposus mesenchymal stem cells. [Method]: Isolate and culture the second generation of normal human nucleus pulposus mesenchymal stem cells (hNPMSCs), and add TNF-α at a concentration of 100ng/ml for 48h. Observe the cell morphology and β-galactosidase staining under the microscope to observe the aging of the cells. CCK-8 detects the cell viability after 1, 3, 5, 7, 9, 11, 13, and 15 days; Western Blot detects aging-related The expression of protein p53 and p16. [Result]: Microscopic observation and β-galactosidase staining showed that hNPMSCs cells were senescent after TNF-α intervention. CCK-8 staining indicated that from the 9th day, hNPMSCs cell proliferation activity was significantly reduced after TNF-α intervention (P<0.05); Western Blot detection showed that the expression of aging-related proteins p53 and p16 was significantly increased after TNF-α intervention (p<0.05). [Conclusion]: High concentration of TNF-α can inhibit the biological activity of hNPMSCs and accelerate cell senescence.