Under the effects of a series of microbial infection and endogenous or exogenous stimuli, inflammasomes are assembled as multiple protein complexes in the cytoplasm, which mainly contain pattern recognition receptors (PRRs), apoptosis-associated speck-like protein containing a CARD (ASC), and pro-caspase-1. The inflammasomes are the platform for caspase-1 activation and subsequent proinflammatory cytokines secretion, and caspase-1 dependent cell death as well. As a key adaptor protein, ASC concatenates PRRs and pro-caspase-1 in the cytoplasm. During inflammasome activation, ASC molecules assemble into large molecule dimers, which is called ASC-speck. The formation of ASC-speck is critical for caspase-1 activation, and ASC-speck becomes a target for the therapy and prevention of inflammatory diseases. In this review, advances in molecular mechanism of ASC-speck formation and the regulation systems for ASC-speck are summarized from the aspects of phosphorylation, ubiquitination and iron channels etc. Finally, the research prospects in this field are discussed.