NLRP3-inflammasome driven inflammation is involeved in the pathogenesis of a variety of disease. A few compounds have been developed to inhibit NLRP3 inflammasome activation, but compounds that are directly and specifically targetting NLRP3 are still not available. Here we show that chemical compound 4-BP specifically inhibited the NLRP3 inflammasome activation in LPS-primed BMDMs, but not AIM2 and NLRC4 inflammasome activations. 4-BP also inhibited caspase-11 mediated non-canonical NLRP3 inflammasome activation induced by LPS transfection. Mechanistically, 4-BP did not affect NLRP3-mediated-loss of mitochondrial membrane potential and tubulin acetylation. 4-BP specifically inhibited NLRP3-mediated ASC oligomerization and translocation of both NLRP3 and ASC from TitonX-100 soluble to insoluble fraction. Prediction by computer calculation methods showed that 4-BP can be combined with NLRP3. Drug affinity responsive target stability (DARTS) assay also substantiated the combining. To investigate the relevance of 4-BP in vivo, we evaluated the effect of 4-BP on MSU-induced peritonitis in mouse model. 4-BP inhibited IL-1β level in peritoneal lavage. Collectively, our data show that 4-BP inhibited NLRP3 inflammasome activation in vitro and in vivo.