Our study displayed that during the progression of CCl4-induced hepatic steatosis and fibrosis, CCl4 induced the expression of NF-κB p65, NLRP3, iNOS, and α-SMA but inhibited the expression of SIRT1; in vitro, with the reduction of SIRT1 expression, NF-κB/NLRP3 pathway was upregulated, along with the high level of Ac NF-κB p65 Lys310 and the release of inflammatory cytokines in LPS-treated RAW 264.7; whereas knockdown of NF-κB or NLRP3 could rescue these effects. Here, NFKB1 is linked to fatty liver disease.