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 tributar…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 tributary Wabash River, extending the southeastern border. Some areas of Southern Illinois are known historically as Little Egypt.