A　limited　number　of　xenobiotic-induced　inflammatory　episodes　occur　in　the　human　liver　and　small　intestine　under　normal　physiological　conditions,　although　many　xenobiotic　agents　are　metabolized　in　these　organs　every　day.　In　this　study,　we　found　that　rifampicin-activated　pregnane　X　receptor　(PXR)　plays　an　important　role　in　the　suppression　of　lipopolysaccharide-activated　nuclear　factor　kappa　B　(NF-kappa　B)　activity　by　increasing　the　expression　of　the　inhibitor　of　kappa　B　alpha　(I　kappa　B　alpha)　in　HepG2　cells.　Rifampicin　did　not　increase　the　expression　of　I　kappa　B　alpha　in　PXR　knockdown　HepG2　cells.　Furthermore,　we　found　that　the　activation　of　PXR　could　inhibit　the　lipopolysaccharide-stimulated　nuclear　translocation　of　NF-kappa　B　p50/p65　using　electrophoretic　mobility　shift　assay,　immunoprecipitation　assays,　and　microscopy.　High　levels　of　I　kappa　B　alpha　directly　interacted　with　NF-kappa　B　and　prevented　its　nuclear　translocation,　thus　inhibiting　its　binding　to　consensus　DNA　sequences　in　nuclei.　Xenobiotic-activated　tissue-specific　PXR　might　exert　anti-inflammatory　actions　by　antagonizing　the　xenobiotic-induced　transcriptional　activity　of　NF-kappa　B　in　the　liver　and　small　intestine.　The　results　also　showed　that　activation　of　PXR　arrested　the　HepG2　cell　cycle　in　the　G(0)/G(1)　phase　and　exhibited　cancer　prevention　potential　by　inhibiting　inflammatory　reactions　in　cells.