The defending Premiership champions face a tough test against the 2010 champions of France, who have made the European crown their principle target in their centenary season.
Sunday's hosts have plenty of incentive heading into the encounter as victory will secure a semi-final (against either Leinster or Cardiff Blues) at Twickenham - meaning they will have two games in a row at the home of English rugby if they can go all the way to the final.
The 2012 final will be the fourth at Twickenham and on each previous occasion an English club has carried off the title.
However, Saracens fell at the semi-final stage in 2008 in their only other appearance in the knock-out stages, while Clermont are attempting to qualify for the semi-finals at the fourth time of asking.
Saracens are boosted by the return of prop Rhys Gill and centre Brad Barritt to their starting line-up.
Meanwhile, scrum-half Richard Wigglesworth makes his first start since October after returning from injury in the clash against Harlequins at Wembley Stadium last weekend.
"Competing with the elite of Europe in the knockout stages of tournaments is where we want to be... both now and in the future," explained Saracens Director of Rugby Mark McCall.
"If you look at the likes of Toulouse, Leicester Tigers, Leinster and Munster, these are teams who have created a legacy in Europe...we want to do the same.
Clermont have put together a highly impressive season, including a 12-game unbeaten run in all competitions, but their form has wavered in recent weeks and their winning streak cam to an end with an uninspired, error-strewn performance last weekend in Biarritz.
The French outfit will be lifted by the news that Morgan Parra makes the starting XV. The French international has recovered from a thigh muscle tear to partner David Skrela in the half-back combination.
Former All Black winger Sitiveni Sivivatu also returns to the side to start out wide.
Saracens: 15 Alex Goode, 14 David Strettle, 13 Owen Farrell, 12 Brad Barritt, 11 Chris Wyles, 10 Charlie Hodgson, 9 Richard Wigglesworth, 8 Ernst Joubert, 7 Will Fraser, 6 Justin Melck, 5 Mouritz Botha, 4 Steve Borthwick (c), 3 Matt Stevens, 2 Schalk Brits, 1 Rhys Gill.
Replacements: 16 Jamie George, 17 Mako Vunipola, 18 Carlos Nieto, 19 George Kruis, 20 Jackson Wray, 21 Neil de Kock, 22 Adam Powell, 23 James Short.
Clermont: 15 Lee Byrne, 14 Sitiveni Sivivatu, 13 Aurelien Rougerie, 12 Wesley Fofana, 11 Julien Malzieu, 10 David Skrela, 9 Morgan Parra, 8 Elvis Vermeulen, 7 Alexandre Lapandry, 6 Julien Bonnaire, 5 Nathan Hines, 4 Jamie Cudmore, 3 Davit Zirakashvili, 2 Benjamin Kayser, 1 Lionel Faure.
Replacements: 16 Ti'i Paulo, 17 Vincent Debaty, 18 Daniel Kotze, 19 Julien Pierre, 20 Julien Bardy, 21 Ludovic Radoslavjevic , 22 Brock James, 23 Jean-Marcel Buttin.
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