We for the first time demonstrated that decreases of ferroptosis-related proteins of HSPB1 and MGST1 are involved in the process of DCM, and further identified that ferroptosis plays an important role in HFD-induced cardiomyocyte injury by bioinformatics analysis of human data, cell and animal experiments. This evidence concerns the gene HSPB1 and familial dilated cardiomyopathy.