The 26-year-old, who was man-of-the-match in Tigers' Guinness Premiership Final demolition of Gloucester, will start on the left-wing as Michael Jones' men look to upset Jake White's South Africa.
After beginning the 2006/07 season outside of the regular Tigers matchday squad, Tuilagi finished the campaign among the most-talked about players in English rugby after a series of powerful performances saw him register 11 tries from just 16 starts.
With the Springboks having put 50 points on England in both of the last two weekends, Samoa will need Tuilagi to transfer his impressive form to the international stage if they are to cause what would be a substantial upset ahead of their World Cup Pool A meeting on September 9.
Jones has made just three changes to the starting 15 that suffered a 27-15 defeat against Australia 'A' in the Pacific Nations Cup tournament last weekend, with captain Brian Lima the only absentee from a full-strength side.
The trio of changes are on the right wing, where Lome Fa'atau replaces David Lemi, on the openside flank, where Justin Purdie comes in for Ulia Ulia, and at hooker, where Mahonri Schwalger takes over from Muliufi Salanoa.
Alesana's younger brother, former Tiger Anitelela who recently moved to Leeds Carnegie, is selected at outside centre.
"This game is an important stepping stone for us and forms part of the bigger picture to the Rugby World Cup," said Jones. "We need these games more than anything. It is a privilege contesting the Pacific Six Nations tournament, but playing South Africa is different. This is the ultimate. We do not have competitions like the Super 14 to see where our players are at. The Springboks are potentially the best team in the world right now and it is a chance of a lifetime, a great privilege, to have this opportunity."
15 Gavin Williams, 14 Lome Fa'atau, 13 Anitelela Tuilagi, 12 Seilala Mapusua, 11 Alesana Tuilagi, 10 Loki Crichton, 9 Steven So'oalo, 8 Semo Sititi (c), 7 Justin Purdie, 6 Daniel Leo, 5 Filipo Levi, 4 Kane Thompson, 3 Census Johnston, 2 Mahonri Schwalger, 1 Justin Va'a
16 Muliufi Salanoa, 17 Donald Kerslake, 18 Iosefa Tekori, 19 Alfie Vaeluaga, 20 Junior Poluleuligaga, 21 Elvis Sevealii, 22 David Lemi