The NLRP3 inflammasome is activated by a variety of external or host-derived stimuli and its activation initiates inflammatory response through caspase-1 activation resulting in inflammatory cytokine IL-1β maturation and secretion. The NLRP3 inflammasome activation is a kind of innate immune response most likely mediated by myeloid cells acting as a host defense mechanism. However, if the activation is not properly regulated, excessive inflammation induced by overactivated NLRP3 inflammasome can be detrimental to the host, causing tissue damage and organ dysfunction, eventually causing several diseases. Previous studies suggested that mitochondrial damage may be a cause of NLRP3 inflammasome activation and autophagy which is a conserved self-degradation process negatively regulates the NLRP3 inflammasome activation. Recently, mitochondria-selective autophagy termed mitophagy has emerged as a central player for maintaining mitochondrial homeostasis by elimination of damaged mitochondria, leading to the prevention of hyperinflammation triggered by NLRP3 inflammasome activation. In this review, we will first focus on the molecular mechanisms of NLRP3 inflammasome activation and the NLRP3 inflammasome-related diseases. And then we will discuss about autophagy especially mitophagy as a negative regulator of the NLPP3 inflammasome activation by examining recent advances in research.