Objective To detect the changes and the clinical significance in plasma protein-complement factor H-related protein 2 (CFHR2) in pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD) children. Methods Various types of 66 CHD patients with or without PAH and 16 healthy children(healthy control group) were studied, including 11 ventricular septal defects(VSD) with PAH (VSD-PAH), 11 isolated VSD, 11 atrial septal defects with PAH (ASD-PAH), 11 isolated ASD, 11 mixed type of heart defects [two or more defects of VSD, ASD and patent ductus arteriosus (PDA)] with PAH (Mix-PAH) and 11 cases without PAH (Mix). CFHR2 was validated by enzyme linked immunosorbent assay in the sample plasma. Results Compared with the healthy control group, the CFHR2 concentration in VSD-PAH patients [(189.10±24.01) μg/L vs.(42.99±4.53) μg/L, t=4.975, P 0.05). The plasma CFHR2 level in Mix-PAH patients [(189.10±24.01) μg/L vs.(83.23±15.96) μg/L, t=3.314, P 0.05] had no difference compared with the healthy control group, but had statistical significance with Mix-PAH group (t=2.370, P<0.05). Conclusions The decrease of CFHR2 protein may demonstrate the deficiency of the immune system and coagulation mechanism in these patients and can be consi-dered as biomarker of CHD-PAH disease. Key words: Pulmonary arterial hypertension; Congenital heart disease; Complement factor H-related protein 2; Biomarker