The Saline River is a tributary of the Ohio River, approximately 27 miles (43 km) long, in the Southern Illinois region of the U.S. state of Illinois. The river drains a large section of southeast Illinois, with a drainage basin of 1,762 square miles (4,564 km2). The major tributaries include the South Fork, Middle Fork and North Fork, all lying within the Saline Valley. The once meandering swampy river was important among Native Americans and early settlers as a source of salt from numerous salt springs where it was commercially extracted in the early 19th century.

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.