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Toll-like receptor (TLRs) is one of the important recognition receptors in the innate immune defense system, which plays a key role in mediating inflammatory response and related signal transduction. In the TLRs family, TLR2/4 has been widely studied because of its close relationship with the occurrence and defense of digestive diseases, and studies have shown that the synergism between TLR2/4 is the basis of mediating inflammatory response and immune response. This article summarizes the research on the correlation of TLR2/4 in digestive system diseases, in order to provide ideas for the clinical treatment and research of digestive system diseases.