Previous studies suggest that TLR4 is the membrane receptor for recognizing LPS. Recent studies have shown that Caspase-11 may play an important role in recognizing cytoplasmic LPS. Upon cytoplasmic LPS binding with Casp-11, Casp-11 activation is observed. Activated Casp-11 directly cleaves gasdermin D, inducing Casp-11-dependent pyroptosis and activates NLRP3/ASC-Casp-1 dependent IL-1β and IL-18 secretion. Besides, it also increases the elimination of Gram-negative bacteria by promoting the fusion of phagosomes and lysosomes. In the process of severe endotoxemia, due to excessive activation of Casp-11, a large number of cells undergo pyroptosis, which lead to intracellular proinflammatory mediators released, induce an uncontrollable inflammatory response, and ultimately lead to the occurrence of endotoxin shock. Casp-11 is a key molecule in endotoxin shock. In this paper, we review the latest progress of Casp-11 in LPS identification, activation and effect in endotoxin.