Objectives: Cold-inducible RNA binding protein (CIRP) is a stress protein which is involved in regulating multiple cellular processes. However, its role in pathological heart diseases is still unknown. Our current study was aimed at addressing the response and functional role of CIRP in heart failure. Methods: CIRP protein level was evaluated in heart samples from patients with heart failure and mice with post-myocardial infarction (post-MI). Cardiac-derived H9C2 cells were utilized to test the effects of CIRP deficiency on cell survival and apoptosis in response to H2O2 treatment. Results: Reduced expression of cardiac CIRP was observed in patients with heart failure, mice with post-MI. In addition, knockdown of CIRP exacerbated cell apoptosis and cell death in response to H2O2 treatment, suggesting a protective role of CIRP in cell apoptosis induced by oxidative stress in the heart. Conclusions: Our findings suggest that altered expression of CIRP may be involved in the pathogenesis of heart failure and downregulation of CIRP may render cardiac cells prone to apoptosis in heart failure. (C) 2019 Published by Elsevier Inc.