Aim To explore the application of carbohydrate antigen 125 （CA125） and amino-terminal pro-brain natriuretic peptide （NT-proBNP） in patients with chronic heart failure. Methods 284 patients with cardiac diseases were divided into four groups （Heart function Ⅰ,Ⅱ,Ⅲ,Ⅳ） according to New York Heart Association （NYHA） class and their serum concentrations of CA125 and NT-proBNP were tested respectively. Then,combined with renal function we respectively compared the level of CA125 and NT-proBNP in the patients with normal renal function or impaired renal function. Results CA125 and NT-proBNP had a significant correlation （r＝0.49,P<0.01） in 284 chosen patients. NT-proBNP concentration was increasing with the level of heart function grade in patients with heart function （Ⅰ,Ⅱ,Ⅲ）（P<0.05）,but NT-proBNP concentration was lower in the patients with heart function Ⅳ than the patients with heart function Ⅲ. However,CA125 concentration was significantly increasing with the level of heart function grade （P<0.05）. In addition combined with renal function,CA125 and NT-proBNP concentration were both significantly increasing with the level of heart function grade （P<0.05） and had a significant correlation （r＝0.700,P<0.01） in 145 patients with normal renal function （eGFR≥60 mL/（min·1.73 m²））. Among 139 patients with impaired renal function （eGFR＜60 mL/（min·1.73 m²））,CA125 and NT-proBNP had a significant correlation （r＝0.292,P<0.01）,NT-proBNP concentration was increasing with the level of heart function grade in patients with heart function （Ⅰ,Ⅱ,Ⅲ） （P<0.05）,but NT-proBNP concentration was significantly lower in the patients with heart function Ⅳ than the patients with heart function Ⅲ （P<0.05）,however CA125 concentration was significantly increasing with the level of heart function grade （P<0.05）. Conclusions Concentration of CA125 and NT-proBNP in serum showed a significant correlation with heart function and could be valuable index in the diagnosis of heart failure. Impaired renal function could interfere with the NT-proBNP concentration,but did not affect the CA125 concentration. Thus,NT-proBNP combined with CA125 would be very useful method to establish diagnosis and treatment in heart failure,especially with renal dysfunction.