The collagen and elastin are important components of extracellular matrix (ECM) in the nucleus pulposus (NP), which can produce water-insoluble proteins through cross-linkages to stabilize ECM. Lysyl oxidase (LOX), a copper-dependent amine oxidase, insolubilizes ECM proteins to keep the stability of ECM by initiating collagen and elastin cross-linkages. The present study aimed to investigate the relationships between intervertebral disc (IVD) degeneration and LOX expression in human NP. A total of 22 cases with lumbar IVD degeneration were designed to the observed group and the control group consisted of 4 young patients with the need of surgically removing the IVD due to lumbar vertebra fracture caused by sudden trauma. These patients were grouped based on Pfirrmann grades of IVDs. The control group represented grade I (group A) and the observed group was subdivided into 4 group: Grade II (group B), grade III (group C), grade IV (group D) and grade V (group E). The herniated NP of each group was prepared for immunohistochemistry, western blotting and reverse transcription-quantitative PCR. The present results showed that the number of NP cells and the components of ECM were significantly lower in the observed group than in the control group. There was an inverse association of the expression rate of LOX NP cells with Pfirrmann grades and age. The protein expression of LOX in group A, B, C, D and E was 2.69±0.24, 2.24±0.32, 1.34±0.19, 1.3±0.32 and 1.01±0.12, respectively. The mRNA expression of LOX in Group A, B, C, D and E was 1±0.03, 0.83±0.07, 0.71±0.09, 0.53±0.09 and 0.27±0.05, respectively. With increasing IVD degeneration, the protein and mRNA expression levels of LOX in NP decreased gradually. Taken together, the findings of the present study revealed that the protein and mRNA expression levels of LOX were decreased with increasing IVD degeneration. These findings provide new insights that LOX might involve in the occurrence and development of IVD degeneration.Copyright: © 2025 Chen et al.