Abstract:[Objective] To investigate the protective effects of Bacillus licheniformis HJ0135 on the liver index, inflammatory cytokines, antioxidant function, and related gene expression of the weaned piglets exposed to lipopolysaccharide (LPS). [Methods] A total of 24 healthy 28-day-old weaned piglets (Duroc×Landrace×Yorkshire) were randomly assigned into 4 groups:control (CON) group, 500 mg/kg B. licheniformis HJ0135 (BL) group, LPS stress (LPS) group, and LPS+500 mg/kg B. licheniformis HJ0135 (BL-LPS) group, with 6 piglets in each group. On day 28 of the experiment, the piglets in the LPS and BL-LPS groups were injected intraperitoneally with 1.5 mL of 1 mg/mL LPS, and those in the CON and BL groups with equal amounts of saline. All the piglets were sacrificed after 1.5 h. [Results] Compared with the CON group, BL treatment decreased the content of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), increased the total antioxidant capacity (T-AOC), the activities of catalase (CAT) and total superoxide dismutase (T-SOD), reduced the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the liver, and up-regulated the expression of CAT, superoxide dismutase 1 (SOD1), SOD2, glutathione peroxidase 1 (GSH-Px1), nuclear factor erythroid 2-related factor (Nrf2), NADPH:quinone oxidoreductase 1 (NQO1), Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor-𝜅B (NF-𝜅B) in the liver. Compared with the LPS group, BL-LPS treatment decreased liver index and serum AST and ALT levels, increased the levels of CAT, GSH-Px, and T-AOC, and reduced the content of malondialdehyde (MDA), interleukin-1β (IL-1β), IL-6, and TNF-α. In addition, BL-LPS treatment up-regulated the mRNA levels of CAT, SOD2, GSH-Px1, Nrf2, TLR4, MyD88, and NF-𝜅B in the liver. [Conclusion] Dietary B. licheniformis HJ0135 can activate the expression of Nrf2 and TLR4-related genes, reduce liver damage and inflammatory cytokine secretion induced by lipopolysaccharide, and improve the antioxidant capacity in weaned piglets.