Background:　The　role　of　thioredoxin-interacting　protein　(TXNIP)　in　lipopolysaccharide-induced　liver　injury　in　mice　has　been　reported,　but　the　underlying　mechanisms　are　poorly　understood.　Methods:　We　overexpressed　deubiquitinase　in　cells　overexpressing　TXNIP　and　then　detected　the　level　of　TXNIP　to　screen　out　the　deubiquitinase　regulating　TXNIP;　the　interaction　between　TXNIP　and　deubiquitinase　was　verified　by　coimmunoprecipitation.　After　knockdown　of　a　deubiquitinase　and　overexpression　of　TXNIP　in　Huh7　and　HepG2　cells,　lipopolysaccharide　was　used　to　establish　a　cellular　inflammatory　model　to　explore　the　role　of　deubiquitinase　and　TXNIP　in　hepatocyte　inflammation.　Results:　In　this　study,　we　discovered　that　ubiquitin-specific　protease　5　(USP5)　interacts　with　TXNIP　and　stabilizes　it　through　deubiquitylation　in　Huh-7　and　HepG2　cells　after　treatment　with　lipopolysaccharide.　In　lipopolysaccharide-treated　Huh-7　and　HepG2　cells,　USP5　knockdown　increased　cell　viability,　reduced　apoptosis,　and　decreased　the　expression　of　inflammatory　factors,　including　NLRP3,　IL-1　beta,　IL-18,　ASC,　and　procaspase-1.　Overexpression　of　TXNIP　reversed　the　phenotype　induced　by　knockdown　USP5.　Conclusions:　In　summary,　USP5　promotes　lipopolysaccharide-induced　apoptosis　and　inflammatory　response　by　stabilizing　the　TXNIP　protein.