〔Abstract〕 Objective To investigate the cross-sectional associations of serum interleukin(IL)-18 with cartilage volume, cartilage defects, bone marrow lesions(BML) and biomarkers of cartilage degradation in patients with knee osteoarthritis(OA), and to provide new ideas and new methods for clinical diagnosis and treatment. Methods The study included 151 patients with knee OA, a general questionnaire survey was conducted, and the knee structural was photographed by magnetic resonance imaging(MRI). The cartilage volume was measured by OsiriX software in 3D-FLASH sequence, and cartilage defect and BML were determined in T2-weighted sequence. Serum IL-18 and matrix metalloproteinase(MMP)-3, 13 levels were measured by enzyme-linked immunosorbent assay(ELISA). SPSS software was used for statistical analysis.Results In multivariable analyses, serum IL-18 level was negatively associated with total cartilage volume(β=-0. 24, 95%CI:-0. 13-0. 03) and the association was consistent at divided part of joint(femorotibial joint and the patella femoral joint, allP<0. 05). Serum IL-18level was positively associated with cartilage defect and BML at media femorotibial area(allP<0. 01). Serum IL-18 level was positively associated with MMP-3(β= 0. 31, 95%CI:0. 001-0. 010) and MMP-13(β= 0. 86, 95%CI:0. 08-0. 10, allP<0. 01).Conclusion Serum IL-18 level is negatively associated with cartilage volume and positively associated with cartilage defect, BML, MMP-3 and MMP-13, suggesting IL-18 may play a significant role in the progression of cartilage degradation in patients with knee OA, the therapy of targeting serum IL-18 may reduce the injury of article cartilage in patients with knee OA and delay the progression of disease.