The 2010 Southern Illinois Salukis football team represented Southern Illinois University Carbondale as a member of the Missouri Valley Football Conference (MVFC) during the 2010 NCAA Division I FCS football season.

Led by third-year head coach Dale Lennon, the Salukis compiled an overall record of 5–6 with a mark of 4–4 in conference play, placing in a six-way tie for third in the MVFC.

Southern Illinois played home games at the newly-opened Saluki Stadium in Carbondale, Illinois.

The following Saluki was drafted into the National Football League following the season.

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