BACKGROUND : The lower back pain (LBP) caused by intervertebral disc (IVD) degeneration brings a heavy burden to society. A classic treatment method of Chinese medicine, fangji-duhuo jisheng decoction (DHJSD), has been effective in the clinical treatment of LBP, although the underlying mechanism remains unknown. OBJECTIVE : In this work, the main objective was to study the effects of DHJSD on in vitro IVD degeneration of human nucleus pulposus (NP) cells after pressure treatment and on an in vivo interrupted IVD degeneration rat model. METHODS : The effects of DHJSD on the viability of NP cells were detected using Cell Counting Kit-8. RT-qPCR, western blotting, TUNEL assay, transmission electron microscopy, and immunofluorescence staining were performed to explore the molecular mechanism underlying protection against compression-induced matrix degradation and apoptosis in NP cells by DHJSD. Furthermore, the effects of DHJSD on IVD degeneration in a rat IDD model were also determined. RESULTS : We found that DHJSD increased the viability of NP cells in a concentration- and time-dependent manner. Furthermore, DHJSD significantly reduced compression-induced NP matrix degeneration and apoptosis, activated autophagy, and inhibited the p38/MAPK signaling pathway in NP cells subjected to compression. Autophagy inhibitor 3-MA and p38/MAPK signaling pathway activator anisomycin reversed the beneficial effects of DHJSD in NP cells, indicating that DHJSD protects against IVD degeneration by autophagy activation and P38/MAPK signaling pathway inhibition. Furthermore, DHJSD treatment effectively delayed IVD degeneration in a puncture-induced IDD rat model. CONCLUSIONS : DHJSD prevents compression-induced matrix degradation and cell apoptosis through regulating autophagy and the P38/MAPK signaling pathway. The mechanism underlying the effects of DHSJD elucidated in this study provides a new direction for LBP treatment.