In the current work, utilizing isolated cardiomyocytes cell lines and animal models of isoproterenol (ISO) infusion, our research elucidated the detrimental role of the miR‐128/MDFI interplay in advancing cardiac hypertrophy and HF, through the upregulation of the Wnt1/β‐catenin signalling axis. This evidence concerns the gene MDFI and cardiac hypertrophy.