IIntervertebral disc(IVD) degeneration(IDD)is a primary cause of low back pain(LBP)in people, which is associated with nucleus pulposus-derived mesenchymal stem cells(NPMSCs). In this study, the involvement of lipopolysaccharide(LPS) in the pyroptosis of NPMSCs was investigated, The effect of RADKPS on the pyroptosis of NPMSCs and the underlying mechanism behind the impact of RADKPS on the proliferative capacity of NPMSCs were also studied.Pyroptosis of NPMSCs was induced with 10 μg/ml LPS and its effects on the downstream signaling pathways were explored. The protective effect of RADKPS on NPMSCs under the action of LPS and its possible mechanism were explored. Usinng different techniques such as immunohistochemical analysis, cell proliferation assay, qPCR, and Western blot analysis. Accordingly, Caspase1/p20/p10, a protein associated with pyroptosis, was found to be over-expressed in LPS-challenged NPMSCs, Furthermore, the qPCR results demonstrated that LPS promoted the expression of pyroptosis-related gene IL-1β(P<0.0001) ,while down-regulated the expression of sox-9(p<0.001),which was a gene associated with the extracellular matrix(ECM). The immunohistochemical results identified lowered ERK1/2 expression and phosphorylated (p-)ERK1/2 in the degenerated IVD tissues. In this study, the influence of RADKPS on the proliferative ability of NPMSCs was evaluated using two-dimensional and three-dimensional cultures. It was noted that RADKPS promoted the proliferation of NPMSCs in the two-dimensional and three-dimensional cultures. The findings of the western blot experiments revealed that RADKPS inhibited the expression of pyroptosis-related proteins, while it upregulated the p-ERK1/2 (p < 0.001), RhoA (p < 0.01), collagen II (p < 0.01), and sox-9 (p < 0.01), while ERK inhibitor PD98059 and RhoA signaling pathway inhibitor CCG-1423 inhibited their expression.These findings reveal to us that RADKPS hydrogel may protect NPMSCs from pyroptosis. It was also noted that cell proliferation-related signaling pathways may promote the proliferation of NPMSCs. The results revealed that RADKPS hydrogel could be used as a potential therapeutic approach for IDD.