The fight is part of "The Ultimate Fighter" Season 16 Finale card, which is slated to be held at the Hard Rock Hotel & Casino in Las Vegas.
Guillard (30-11-2, one no-contest) put together a six-fight win streak that raised talk last year of him possibly landing a title shot. But a first-round submission loss to Joe Lauzon on Oct. 8, 2011, ended that conversation.
He has since dropped two of his three most recent bouts, including a first-round knockout loss on Aug. 11 to Donald Cerrone.
Varner is a former WEC lightweight champion. He has a professional mixed martial arts record of 20-7-1 with two no-contests.
The fight against Guillard will mark Varner's third with UFC since his return to the promotion in May, when he upset highly touted Edson Barboza via first-round TKO.
Varner was submitted by Lauzon in the third round on Aug. 4.