Inflammasomes are cytosolic protein complexes composed of innate immune sensors, the adaptor protein ASC, and the cysteine protease caspase-1. In response to microbial infection or ‘danger signals', inflammasomes play critical roles in host defense or contribute to the pathogenesis of various inflammatory diseases. Recent studies have provided abundant evidence for a vital role of phosphorylation in the regulation of inflammasome assembly and activation. This review integrates previous observations and discoveries for inflammasome regulation by protein phosphorylation with the most recent findings. Additionally, the timely application and clinical prospects in the treatment of inflammatory diseases, by targeting related protein kinases or phosphatases, are also discussed.