Abstract: Objective　To study the changes and clinical significance of serum heart-type fatty acid-binding protein (H-FABP) and soluble ST2 protein (sST2) in children with chronic heart failure (CHF). Methods　Thirty-nine children with CHF and 30 healthy children were recruited. Serum levels of H-FABP and sST2 were determined by ELISA, The left ventricular ejection fraction (LVEF) and fractional shortening of the left ventricle (LVFS) were measured by two-dimensional echocardiography. Results　In 39 children with CHF, 15 males and 24 females, aged 2 months to 14 years, included 27 cases of endocardial fibroelastosis (EFE) and 12 cases of dilated cardiomyopathy (DCM). According to the cardiac functional grading standard, the children with CHF were divided into 10 cases with cardiac function II, 15 cases with cardiac function III, and 14 cases with cardiac function IV. The mean levels of H-FABP, sST2 and NT-Pro-BNP in children with CHF at stage of heart failure and heart failure remission were statistically higher than those in the healthy children (all P<0.01). The serum H-FABP and sST2 levels had significant differences among groups grouped according to cardiac functional grading standard (all P<0.05). The serum H-FABP and sST2 levels had no significant difference between the EFE and DCM groups (all P>0.05). The Spearman correlation analysis showed that, in children with CHF at stage of heart failure, the serum H-FABP level was positively correlated with NT-Pro-BNP, sST2 and cardiac function (r=0.402、0.621、0.644, P<0.05). Serum sST2 level was positively correlated with NT-Pro-BNP and cardiac function (r = 0.501、 0.678, P<0.05), and was negatively correlated with LVEF and LVFS (r= − 0.340、− 0.329, P<0.05). Conclusions　H-FABP and sST2 are involved in the development of heart failure. H-FABP and sST2 can be used as reference indices for clinical diagnosis and assessment of CHF.