Springboks centre de Villiers was this week confirmed as captain for the three-Test series against England which begins in Durban on Saturday.
De Villiers has 72 caps and will partner another experienced performer in Frans Steyn, who has made 47 appearances, but he is anticipating a stern examination from England's centres.
The explosive Tuilagi has been identified as one of England's most likely potential match-winners and his new partnership with South African-born Barritt showed potential in this year's RBS 6 Nations.
De Villiers, 31, said: "Manu Tuilagi has shown he is a massive threat on attack and defensively he is very solid as well.
"He has really formed a great partnership with Brad Barritt.
"Frans and I will have our work cut out tomorrow. It is going to be a tough day at the office but it is a challenge we are looking forward to.
"We are representing our country, they are representing theirs and that is what Test match rugby is all about.
"It is putting your bodies on the line and digging in for your country."
De Villiers has dismissed fears the Springboks might be under-prepared going into their first match under new coach Heyneke Meyer at Kings Park.
Meyer's new-look squad only assembled for the first time earlier this week after a round of Super 15 matches last weekend.
De Villiers said: "I really think we have had a fantastic week preparation-wise.
"We have only had three days but the camps Heyneke did during the year with the franchises has really worked and we are reaping the rewards now."
South Africa, after a number of retirements and injuries, will begin the Meyer era with three new caps in their pack in flanker Marcell Coetzee and locks Juandre Kruger and Eben Etzebeth.
De Villiers said: "For those guys making their debuts, it is a great a honour.
"They know they have worked hard to get here and they know all they need to do now is perform in the way they did for their franchises, then everything will go well on Saturday.
"I think when you represent your country there is always pressure and there is obviously a lot of pressure for tomorrow's game.
"But I don't think we are focusing on the result now. We know what we need to do as a team to perform well and hopefully then get the result."
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