Post-myocardial infarction (MI) cardiac remodeling ultimately causes heart failure. We explored how CUG-binding protein Elav-like family member 1 (CELF1) affected post-MI cardiac remodeling. Mice underwent MI induction by left anterior descending artery (LAD) ligation and short hairpin-CELF1, overexpressing-flavin-containing monooxygenase 2 (FMO2) lentivirus and transforming growth factor-β1 (TGF-β1) treatments. Mouse cardiac fibroblasts were cultured in vitro, followed by fibrosis induction with TGF-β1. Left ventricular ejection fraction, left ventricular end-diastolic volume and left ventricular end-systolic volume were tested by ultrasound cardiography. Heart weight/body weight was determined. CELF1 and FMO2 mRNA levels, pathologic changes, collagen deposition and myocardial fibrosis of cardiac tissues, cardiomyocyte area, myocardial apoptosis, and myocardial CELF1, FMO2, collagen I, fibronectin, and elastin levels were assessed by RT-qPCR, HE, Masson, WGA, TUNEL staining, and immunohistochemistry. CELF1-FMO2 interaction was confirmed using RNAct database and RIP assay. The biotinylated GU-rich element of FMO2 mRNA-CELF1 binding and mRNA stability were assayed by RNA pull-down and actinomycin D assays. LAD ligation induced cardiac remodeling [cardiac enlargement, myocardial tissue damage, increased myocardial collagen fiber tissues, poor cardiac function, cardiomyocyte hypertrophy, myocardial apoptosis, and extracellular matrix (ECM) deposition]. CELF1 was up-regulated in post-MI mouse myocardial tissues. CELF1 silencing up-regulated FMO2 and improved previously-mentioned conditions in MI mice, which were partially reversed by inducing ECM deposition. CELF1 down-regulated FMO2 and promoted FMO2 mRNA decay through interaction with FMO2 and FMO2 mRNA 3'UTR, respectively. FMO2 overexpression improved ECM deposition and cardiac remodeling in MI mice. CELF1 facilitates post-MI cardiac remodeling through FMO2 inhibition.