Southern Illinois is a region of the U.S. state of Illinois comprising the southern third of the state, principally south of Interstate 70. Part of downstate Illinois, it is bordered by the two most voluminous rivers in the United States: the Mississippi below its connection with the Missouri River to the west and the Ohio River to the east and south, with the Wabash as a tributary. Some areas of Southern Illinois are known historically as Little Egypt.

Southern Illinois University is a public research university in Carbondale, Illinois. Chartered in 1869, SIU is the oldest and flagship campus of the Southern Illinois University system. SIU enrolls students from all 50 states and more than 100 countries. Originally founded as a normal college, the university today provides programs in a variety of disciplines, combining a strong liberal arts tradition with a focus on research. SIU was granted limited university status in 1943 and began offering graduate degrees in 1950. A separate campus was established in Edwardsville, Illinois in 1957, eventually becoming Southern Illinois University Edwardsville.