Abstract: Francisella tularensis, the causative agent of zoonotic disease tularemia, is a facultative intracellular growth gram negative bacterium that infects more than 250 species of animals. It is one of the most contagious pathogens known in human medical history. Humans could be contracted via various routes including (i) by bite of arthropods such as ticks, flies and mosquitoes, (ii) by direct contact with infected animals and their tissues or body fluids, (iii) by ingestion of the contaminated drinking water or food, and (Ⅳ) by inhalation of the contaminated aerosol. Due to its extreme low infectious dose, high mortality, stability under dry conditions and proneness to be aerosolized, F. tularensis was utilized as a bacterial biological weapon during the cold war and the World War Ⅱ. The virulence of F. tularensis is fully depended on its ability of phagosome escaping and intracellular replication. A non-canonical type Ⅵ secretion system(T6SS)encoded by the F. tularensis pathogenicity island (FPI) is essential for its phagosome escaping, intracellular replication and pathogenicity to animals. This paper summarizes the progress in research of the FPI-coded T6SS of F. tularensis.