De Villiers, who joined reigning Magners League champions Munster from Western Province in September, will line up alongside 2009 Lions Keith Earls, Ronan O'Gara, Donncha O'Callaghan and John Hayes when Munster take on Leinster at the Royal Dublin Showground.
Lions skipper Paul O'Connell is likely to make an appearance from the replacements bench, as is fellow 2009 Lion David Wallace.
De Villiers will face yet another midfield battle against Lions stalwart Brian O'Driscoll after the Ireland captain was named in the Leinster side for the first time this season.
O'Driscoll and de Villiers wore their teams' No13 and No12 shirts respectively during both the first and second Tests between the Lions and Springboks in June of this year.
And de Villiers, who won more than 50 caps for South Africa before moving to Munster, has paid his rival the ultimate compliment ahead of today's highly-anticipated clash.
"It's always good to play the top players in world rugby," said De Villiers.
"And I don't think they come much better than Brian O'Driscoll."
De Villiers will also face O'Driscoll's Lions team-mates Gordon D'Arcy, Luke Fitzgerald, Jamie Heaslip and Nathan Hines right from the start at the RDS, while Rob Kearney is expected to come on as a replacement at some stage in the Irish derby.
With such quality in the opposition ranks, particularly in a Lions heavy backline, de Villiers knows his focus cannot simply be on O'Driscoll.
"Rob Kearney was someone who really impressed me," added de Villiers.
"I hadn't seen much of him beforehand but I thought he was tremendous in that second Test, absolutely phenomenal.
"Obviously, Luke Fitzgerald is a quality player. Then there's Gordon D'Arcy, quality players, we'll have to be on top of our game."
Tomas O'Leary, the Ireland scrum-half, and Jerry Flannery, Ireland's first-choice hooker, who were both selected for the Lions tour before injury prevented them from travelling to South Africa, are set to feature. O'Leary continues his comeback from a fractured ankle with a another start for Munster, while Flannery earns a spot on the bench following an elbow injury.
Munster: 15 Keith Earls, 14 Doug Howlett, 13 Lifeimi Mafi, 12 Jean de Villiers, 11 Denis Hurley, 10 Ronan O'Gara (captain), 9 Tomas O'Leary, 8 Nick Williams, 7 Niall Ronan, 6 Denis Leamy, 5 Mick O'Driscoll, 4 Donncha O'Callaghan, 3 John Hayes, 2 Denis Fogarty, 1 Marcus Horan
Replacements: 16 Jerry Flannery, 17 Tony Buckley, 18 Paul O'Connell, 19 David Wallace, 20 Paul Warwick, 21 Peter Stringer, 22 Ian Dowling
Leinster: 15 Isa Nacewa, 14 Shane Horgan, 13 Brian O'Driscoll, 12 Gordon D'Arcy, 11 Luke Fitzgerald, 10 Jonathan Sexton, 9 Eoin Reddan, 8 Jamie Heaslip, 7 Shane Jennings, 6 Kevin McLaughlin, 5 Nathan Hines, 4 Leo Cullen (captain), 3 Stan Wright, 2 John Fogarty, 1 Cian Healy
Replacements: 16 Bernard Jackman, 17 Mike Ross, 18 Malcolm O'Kelly, 19 Sean O'Brien, 20 Simon Keogh, 21 Fergus McFadden, 22 Rob Kearney