The 2016 Southern Illinois Salukis football team represented Southern Illinois University Carbondale as a member of the Missouri Valley Football Conference (MVFC) during the 2016 NCAA Division I FCS football season.

Led by first-year head coach Nick Hill, the Salukis compiled an overall record of 4–7 with a mark of 2–6 in conference play, placing in a three-way tie for eighth in the MVFC.

Southern Illinois played home games at Saluki Stadium in Carbondale, Illinois.