Abstract Objectives Kawasaki disease (KD) is an acute immune-mediated vasculitis primarily affecting coronary arteries, with limited specific diagnostic biomarkers available. Chitinase protein-40 (YKL-40), a glycoprotein secreted by neutrophils and macrophages, has been associated with vascular inflammation in cardiovascular diseases. This study aimed to investigate the role of YKL-40 in KD by analyzing its serum levels, correlations with inflammatory markers, and potential as a diagnostic and prognostic biomarker. Methods Serum YKL-40 and interleukin-6 (IL-6) levels were measured using enzyme-linked immunosorbent assay (ELISA) in 46 children with KD (16 with coronary artery lesions [CAL], 30 without CAL) and 30 healthy controls. Correlations between YKL-40, IL-6, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell (WBC) count, and platelet (PLT) levels were analyzed. Results YKL-40, IL-6, CRP, ESR, WBC, and PLT levels were significantly elevated in KD patients compared to controls. YKL-40 levels correlated positively with IL-6, CRP, and ESR. A serum YKL-40 threshold of ≥ 71.930 ng/mL predicted CAL with sensitivity and specificity of 0.875 and 0.800, respectively. Combining YKL-40 with IL-6 improved sensitivity and specificity to 0.938 and 0.833. Conclusions YKL-40 is significantly elevated in KD and correlates with inflammatory markers, suggesting its involvement in disease pathogenesis. It is a promising inflammatory biomarker and independent risk factor for predicting CAL in KD, offering potential for improved diagnosis and prognosis. Clinical trial number Not applicable.