Illinois Route 351 is a north–south state route that leads from Illinois Route 71 and Illinois Route 251 by Oglesby through downtown LaSalle to Interstate 80. It is 8.55 miles (13.76 km) long.

Illinois 351 is the former Business U.S. Route 51 through La Salle. It crosses over the Illinois River on the Shippingsport Bridge south of La Salle and passes underneath the Abraham Lincoln Memorial Bridge as it climbs out of the Illinois River Valley. Like Illinois Route 251, Illinois 351 can be considered a spur off its parent, U.S. Route 51.

Prior to 1963, U.S. Route 51 ran along this route. From 1963 to 1966, it became Business U.S. 51 as U.S. 51 was rerouted onto a new freeway to the east of La Salle. In 1966, this was changed again to Illinois Route 351.