AbstractDiagnosis of central precocious puberty (CPP) in girls remains a huge challenge. The current study was to measure the serum expression of methyl-DNA bind protein 3 (MBD3) in CPP girls and assess its diagnostic efficacy. To begin with, we enrolled 109 CPP girls and 74 healthy pre-puberty girls. Then, MBD3 expression in their serum samples was measured via reverse transcription-quantitative polymerase chain reaction, and its diagnostic efficacy on CPP was assessed via the receiver operating characteristic (ROC) curve, followed by correlation analysis between serum MBD3 and patient age, gender, bone age, weight, height, body mass index, basal luteinizing hormone (LH), peak LH, basal follicle-stimulating hormone (FSH), peak FSH, and ovarian size using bivariate correlations method. Finally, independent predictors of MBD3 expression were confirmed using multivariate linear regression analysis. MBD3 was highly expressed in sera of CPP patients. The area under the ROC curve of MBD3 diagnosing CCP was 0.9309, with 1.475 cut-off value (92.66% sensitivity and 86.49% specificity). MBD3 expression positively correlated with basal LH, peak LH, basal FSH, and ovarian size, among which basal LH was considered the strongest independent predictor of MBD3, followed by basal FSH and peak LH. In summary, serum MBD3 could act as a biomarker in aiding CPP diagnosis.