Objective: To study the value of serum growth differentiation factor-15 (GDF-15) combined with B-type natriuretic peptide (NT-proBNP) in the diagnosis and prognosis of heart failure. Methods: Sixty-eight patients with heart failure from July 2017 to July 2018 were selected. The NYHA classification was divided into 40 patients with mild heart failure (NYHA class I-II) and 38 patients with severe heart failure (NYHA class III-IV). The value of GDF-15 and NT-proBNP for diagnosing heart failure was studied with an ROC curve. The prognostic value of GDF-15 and NT-proBNP in heart failure was discussed according to the outcomes of the follow-up group. Results: The serum GDF-15 and NT-proBNP levels in patients with mild heart failure and patients with severe heart failure were higher than those of the control group (P<0.01). The serum GDF-15 and NT-proBNP levels in patients with severe heart failure were higher than those with mild heart failure (P<0.01). The AUC of GDF-15 in the ROC curve was 0.885 (95% CI = 0.812-0.954), and the best diagnostic node was 916.26 ng/L, with corresponding sensitivity and specificity of 7836% and 8129%, respectively. The AUC of NT-proBNP for diagnosing heart failure was 0.912 (95% CI: 0.864-0.968), and the best diagnosis node was 1623 28 ng/L. The corresponding sensitivity and specificity were 82.16% and 89.52%, respectively. The AUC of GDF-15 + NT-proBNP for diagnosing heart failure was 0.953 (95% CI: 0.891-0.992), and its sensitivity and specificity were 89.73% and 92.14%, respectively. The value of GDF-15 combined with NT-proBNP in diagnosing heart failure was the highest. In the follow-up year, the mortality and readmission rate of the heart failure group were higher than those of the control group (P<0.01). Additionally, the GDF-15 and NT-proBNP levels in the poor prognosis group were higher than those in the patients with good prognosis (P<0.01). The AUC of GDF- 15 in the analysis of the ROC curve was 0.849 (95% CI: 0.785-0.893), and the sensitivity and specificity were 8636% and 8036%, respectively. The AUC of NT-proBNP in the treatment of heart failure was 0.801 (95% CI: 0.749-0.865), and the sensitivity and specificity were 83.69% and 7536%, respectively. The AUC of GDF-15 NT-proBNP in diagnosing heart failure was 0.897 (95% CI: 0.815-0.932), and the sensitivity and specificity were 8936% and 81.14%, respectively. Among these, the value of GDF-15 combined with NT-proBNP in evaluating the prognosis of heart failure was the highest. Conclusion: GDF-15 and NT-proBNP can be used as a test index for diagnosing heart failure and evaluating its prognosis. The value of GDF-15 and NT-proBNP in the diagnosis and prognosis of heart failure is the highest.