Chronic inflammation without microbial infection, termed sterile inflammation, plays crucial roles in the development of heart failure. Mechanistically, the process of sterile inflammation starts with the sensing of damage-associated molecular patterns (DAMPs) via multiple pattern recognition receptors. These processes lead to the activation of NF-κB, which induces transcriptional activation of inflammatory cytokines and NLRP3, as a priming process of sterile inflammation. Subsequently, NLRP3 is activated and forms a protein complex termed the inflammasome, resulting in the generation of bioactive IL-1β. In this process, mitochondria play key roles by providing a signaling platform as well as generating mitochondrial DAMPs. In this review, we summarize the current evidence regarding the role of mitochondria in sterile inflammation, specifically in the heart.