As an indispensable virulence determinant, Salmonella pathogenicity island 1(SPI-1) has gained much attention in host-pathogen interactions. More and more studies on SPI-1 have demonstrated that it is far more complex than the one we used to expect. It not only affects sophisticated activities during infection, including invasion, replication, and host responses, but also extends to other fields like biofilm formation. In addition, mutants in SPI-1 effectors have been explored as vaccines, the effective ways to prevent salmonellosis. The activity of SPI-1 is influenced by many factors which have been widely reported. Investigations on these factors may provide new insights into prevention and treatment of salmonellosis. Therefore, SPI-1 is a tempting issue worthy of further exploration. In this review, we will probe into SPI-1 systematically.