With galectin-3 playing an important role in inflammatory responses, elevated galectin-3 levels have been shown in patients with autoimmune diseases. However, there are limited data regarding galectin-3 expression in patients with autoinflammatory diseases such as adult-onset Still's disease (AOSD). This study aimed to investigate the extracellular galectin-3 expression and examine its association with activity parameters and disease outcome in AOSD patients. Plasma levels of galectin-3 and inflammasome downstream cytokines including interleukin (IL)-1β and IL-18 were determined by ELISA in 42 active AOSD patients and 20 healthy controls (HC). The protein levels of galectin-3 and cytokines were determined using immunoblotting. Plasma levels of galectin-3 and inflammasome downstream cytokines including IL-1β and IL-18 were significantly higher in AOSD patients (median 5.02ng/ml, interquartile range [IQR] 3.12-7.88ng/ml; 3.42pg/ml, IQR 1.48-6.70pg/ml; and 5758pg/ml, IQR 859-11,895pg/ml, respectively) compared with HC (1.86ng/ml, IQR 1.09-2.89ng/ml; 0.99pg/ml, IQR 0.62-1.35pg/ml; and 129pg/ml, IQR 71-155pg/ml, respectively, all p < 0.001). Plasma galectin-3 levels were positively correlated with clinical activity scores, inflammatory parameters values, and the levels of IL-1β and IL-18 in AOSD patients. AOSD patients with systemic pattern had significantly higher galectin-3 levels (median 6.08ng/ml, IQR 4.01-9.54ng/ml) compared with those with chronic articular pattern (3.56ng/ml, IQR 3.04-4.98ng/ml, p < 0.05). After 6-month therapy, galectin-3 levels significantly declined, paralleling the decreases in clinical activity scores and plasma levels of IL-1β and IL-18. Elevated galectin-3 levels and their positive correlation with disease activity scores, inflammatory parameter, and inflammasome downstream cytokines suggest the involvement of galectin-3 in AOSD pathogenesis.Key Points• We revealed for the first time the association of plasma galectin-3 levels with AOSD activity parameters.• We explored the link between galectin-3 levels and NLRP3-inflammasome downstream cytokines in AOSD disease.