Abstract: Lipopolysaccharide (LPS)-induced bone marrow-derived macrophages (BMDMs), treated with licochalcone A (LCA) and retreated with inflammasome inducers respectively (ATP and nigericin), were used to construct the inflammasome model of NLRP3 (NOD-like receptor family, pyrin domain containing 3), to investigate the inhibitory effect and the molecular mechanism of LCA on the activity of NLRP3 inflammasome. The secretion of mature interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) and caspase-1 in the supernatants were analyzed by ELISA and the Caspase-Glo^® 1 Inflammasome Assay. Supernatants and cell lysates were analyzed for the expression of pro-caspase-1, pro-IL-1β, ASC, NLRP3, IL-1β, caspase-1 by immunoblotting. The study shows that LCA inhibited the activity of caspase-1 and the secretion of IL-1β, and suppressed the activity of NLRP3 inflammasome. There was also slight inhibition of NLRC4 inflammasome induced by Lfn-Flic, but no effect on poly(dA:dT)-induced the absent in melanoma 2 (AIM2) inflammasome. Western blot showed that LCA had no effect on the protein expression of NLRP3 and pro-IL-1β, which was mediated by NF-κB pathway. In summary, LCA can inhibit the cleavage of pro-caspase-1 and suppress the secretion of IL-1β to reduce the inflammation response. The study was carried out under the approval of the Scientific Investigation Board of 302 Hospital of PLA.