Long non-coding RNAs (lncRNAs) have been reported to be involved in the development of various cardiovascular diseases, including chronic heart failure (CHF). In this study, we aimed to investigate the role of ZFAS1/miR-590-3p axis in the diagnosis and prognosis of CHF. The expression of ZFAS1 and miR-590-3p in the serum samples of CHF was measured using quantitative real-time polymerase chain reaction. Pearson correlation coefficient was applied to analyze the correlation between ZFAS1 and miR-590-3p. The receiver operating characteristic (ROC) curve was used to examine the diagnostic accuracy of ZFAS1, miR-590-3p, and brain natriuretic peptide (BNP). The Kaplan-Meier curve and Cox regression analysis were used to assess the prognostic value of ZFAS1 and miR-590-3p in CHF. This study found that the serum levels of ZFAS1 were significantly higher, while miR-590-3p levels were significantly lower in CHF. ROC results indicated that the combined diagnostic accuracy of ZFAS1 + miR-590-3p + BNP was significantly higher than that of these indicators used alone. Kaplan- Meier results showed that patients with low expression of miR-590-3p or high expression of ZFAS1 had poor prognosis. In conclusion, CHF patients had increased ZFAS1 and decreased miR-590-3p expression. ZFAS1 and miR-590-3p might serve as novel non-invasive diagnostic and prognostic markers for patients with CHF.