Objective: To investigate the mechanism by which TANK binding kinase 1 (TBK1) regulates the activation of NLRC4 (nucleoside binding oligomerization domain like receptors, NLRC4) inflammasomes. Method: Protein immunoblotting was used to detect the activation of NLRC4 inflammasomes and their downstream molecules caspase-1 and Gasdermin D in bone marrow derived macrophages (BMDMs) or immortalized bone marrow macrophages (iBMDMs) infected with Salmonella typhimurium (S.T); Using a lactate dehydrogenase detection kit to detect the content of lactate dehydrogenase in the supernatant of cell culture medium; Determine the interaction between TBK1 and NLRC4 and the specific interaction domain through protein immunoprecipitation experiments; Cellular immunofluorescence assay was used to determine the spatial localization of TBK1 and NLRC4. The GST pull down experiment confirmed the direct interaction between TBK1 and NLRC4; Verify the assembly of NLRC4 inflammasomes using ASC oligomerization detection experiments. Build S T infected animal model was used to observe the survival of mice. Analyze the bacterial load of organs such as the lungs through smear analysis; Detection of TNF in ascites and serum using enzyme-linked immunosorbent assay (ELISA)- α And IL-1 β Content of; Flow cytometry was used to detect the proportion of neutrophils in peritoneal lavage fluid. Result: In S In T infected bone marrow macrophages, inhibiting TBK1 can lead to weakened activation of NLRC4 inflammasomes, decreased phosphorylation levels of NLRC4, and reduced cleavage of pro caspase-1 and Gasdermin D; There is an interaction between TBK1 and NLRC4, and the N-terminal of TBK1 interacts with the NACHT domain of NLRC4; TBK1 and NLRC4 have spatial co localization; TBK1 can phosphorylate the NLRC4Ser533 site. S. T animal model experiments showed that inhibiting TBK1 activity can significantly improve the survival rate of mice; Weakening the bacterial load in the organs of mice; Reduce IL-1 in serum and ascites β， TNF- α； Reduce the proportion of neutrophils in peritoneal lavage fluid. Conclusion: TBK1 interacts with NLRC4, phosphorylates the NLRC4S533 site, and promotes the activation of NLRC4 inflammasomes. The mechanism by which TBK1 participates in the regulation of NLRC4 inflammasome and its role in NLRC4 inflammasome related diseases was elucidated, providing theoretical basis and new potential targets for the treatment of related diseases.