Objective:To observe the clinical significance of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and Cystatin C (Cys-C) in diagnosing elderly patients with chronic heart failure (CHF) and evaluating classification of cardiac function and prognosis. Methods: A total of 178 elderly patients with CHF were selected as the observation group, including 35 cases of cardiac function grade Ⅰ, 47 cases of gradeⅡ, 64 cases of grade Ⅲ, 32 cases of grade Ⅳ according to New York Heart Association Functional Classification (NYHA), and 87 healthy people taking health examination were selected as the healthy control group. NT-proBNP and Cys-C levels were detected, and left ventricular end-diastolic diameter (LVEDD), 1eft ventricular ejection fraction (LVEF) were measured. NT-proBNP and Cys-C levels were compared between the observation group and the healthy control group, and between patients with different cardiac function grades. Logistic regression analysis was performed to analyze the influencing factors of death end events in elderly patients with CHF, and the correlation among NT-proBNP, Cys-C and LVEDD, LVEF was analyzed by using Spearman correlation statistics. Results: NT-proBNP level, Cys-C level and LVEDD in the observation group were higher than those in the healthy control group, LVEF in the observation group was lower than that in the healthy control group (P < 0.05). NT-proBNP, Cys-C, and LVEDD were gradually increased from cardiac function grade Ⅰ to grade Ⅳ, while LVEF was gradually decreased (P < 0.05). Logistic regression analysis showed that NT-proBNP, Cys-C, and LVEF were risk factors of death of elderly CHF patients (P < 0.05). Correlation analysis showed that NT-proBNP was positively correlated with LVEDD (r=0.824, P < 0.05), while negatively correlated with LVEF (r=-0.723, P < 0.05), Cys-C was positively correlated with LVEDD (r=0.797, P < 0.05), while negatively correlated with LVEF (r=-0.714, P < 0.05). Conclusion: NT-proBNP and Cys-C level are useful in diagnosing elderly CHF patients and evaluating classification of cardiac function, and have certain predictive value for prognosis of elderly CHF patients.