Objective To address the levels of serum miR-21/155/181a/18b in dilated cardiomyopathy (DCM) patients at a progressive heart failure stage. Methods The serum miRNAs were measured by real-time reverse-transcription PCR in 40 DCM patients and in 30 healthy controls. Pearson's correlation coefficient was used to calculate the potential correlation between miRNAs and other indicators, such as human N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hsCRP), left ventricular ejection fraction (LVEF%), and left ventricular end-diastolic diameter (LVEDD). Results Our findings revealed that serum miR-21 were significantly reduced in DCM patients compared with the healthy controls(P<0.01). We also found that serum miR-21 was positively correlated with LVEF% and negatively correlated with LVEDD (P<0.001). Conclusion The serum level of cardiac remodeling-associated miR-21 is decreased in DCM patients at a progressive heart failure stage compared to the healthy controls, which may be also related to the disease severity.