Salmonella infection which generally spread via food, is a serious threat to human health. As an important barrier against Salmonella invasion, intestinal epithelial cells reduce the colonization and invasion of Salmonella in multiple ways. At the same time, intestinal mononuclear phagocytes also recognize Salmonella through NAIP, which activates NLRC4 inflammasome to induce pyroptosis and Salmonella elimination. Caspases are a family of cysteine-aspartic proteases that carry out a variety of cellular functions. Pyroptosis mediated by Caspase-1 is the key component of inflammasomes, which induces pyroptosis by cleaving gasdermin D. Previous research found that, just like caspase-1, caspase-8 was also recruited by inflammasomes, but its function was unclear. Recent research revealed that, when pyroptosis was inhibited, Caspase-8 could be strongly activated in inflammasomes of intestinal epitheliums and macrophages which protected against Salmonella infection. Therefore, Caspase-8 can also be a key molecule to regulate host anti-infection immunity during Salmonella infection, and the mechanism of Caspase-8 in regulating host cell death is of great significance for further understanding the relationship between Salmonella infection and host anti-infection immune response.