One main cause of persistent back discomfort is intervertebral disc degeneration (IDD), with inflammation and extracellular matrix (ECM) degradation playing critical roles. This study investigates the role of ZIP8, a zinc transporter, in IDD pathogenesis, focusing on its effects on inflammatory responses, ECM degradation and Wnt/β-catenin signalling pathway. ZIP8 was identified as a hub gene from the GSE27494 dataset through bioinformatics analysis. The role of ZIP8 was investigated in nucleus pulposus (NP) cells and RAW 264.7 macrophages. An in vivo IDD rat model was used to assess the consequences of ZIP8 overexpression. The involvement of the Wnt/β-catenin pathway was examined, and the effect on macrophage polarisation was analysed. ZIP8 overexpression in NP cells led to increased inflammatory cytokine production and enhanced NF-κB pathway activation, while ZIP8 knockdown alleviated these effects. In vitro, ZIP8 knockdown reduced IL-1β-induced apoptosis and ECM degradation, promoting cell viability. In vivo, ZIP8 overexpression exacerbated disc degeneration, as evidenced by magnetic resonance imaging (MRI) and histological assessments. Additionally, modulation of ZIP8, in conjunction with the Wnt/β-catenin signalling pathway, revealed its involvement in regulating apoptosis and proliferation in NP cells. In RAW 264.7 macrophages, ZIP8 knockdown inhibited M1 macrophage polarisation and reduced proinflammatory cytokine expression, while promoting anti-inflammatory responses. ZIP8 is a key regulator in IDD, affecting inflammation, ECM integrity and Wnt/β-catenin signalling pathways. Targeting ZIP8 by knockdown may offer therapeutic potential in IDD by modulating inflammatory responses and protecting ECM structure, offering a novel approach to IDD treatment.