Up to date, there has been no molecular signature available in the clinical practice for attention-deficit/hyperactivity disorder (ADHD). To investigate circulating miRNA let-7d significance in ADHD, we investigated serum miRNA let-7d in 35 newly diagnosed ADHD subjects who were randomly selected from 406 patients out of 7450 children, paired with gender- and age-matched control through case-control study. We observed that circulating miRNA let-7d was significantly higher in ADHD subjects than in control (p < 0.05). Higher circulation level of miRNA let-7d was significantly associated with ADHD (odds ratio 16.7; 95% confidence, p < 0.05). Meanwhile, serum galectin-3 level was down-regulated in ADHD subjects and the subjects with low galectin-3 expression accounted for 66% in ADHD. The difference of the serum galectin-3 levels between ADHD and non-ADHD groups reached significance (p < 0.05). In 1-year follow-up, a significantly higher rate of clinical improvement was noted in subjects with low level of circulating miRNA let-7d (p < 0.05) than those with high level of circulating miRNA let-7d. Our data demonstrated that miRNA let-7d was elevated in the serum of ADHD subjects, which might be a novel, useful molecule signature for ADHD.