The 27-year-old Stormers and Western Province player has been named in the starting line up for the Boks' clash with Wales at the Millennium Stadium where he and fellow centre Adrian Jacobs will go head-to-head with Gavin Henson and Jamie Roberts.
Henson featured in the second Test for the Lions in New Zealand three years ago, while Roberts is starting in his fourth different position in as many matches for Wales.
"I've never played directly against Gavin but he's a quality centre with all the skills," said de Villiers, who made his Springbok debut against France back in 2002 but then had to wait until 2004 to win his second international cap.
"Wales play much better when he's in their team but he hasn't played many games.
"Gavin has the experience of playing for the British & Irish Lions and I'm sure he will want to perform with places up for grabs to face us next year.
"Jamie played in Pretoria and he's a big man who runs straight and hard. They will use him to move forward in midfield and will be difficult to bring him down.
"As a combination Wales have got it spot on with Gavin as a creator and distributor with Jamie as the big man outside him."
De Villiers has already faced Wales on two occasions so far this year, scoring three tries as the World Champions secured a 2-0 series victory during the summer. An ankle injury ensured Henson was a notable absentee during the matches in South Africa, however, and de Villiers expects a tougher examination this time around.
"We've done pretty well this year and held the upper hand back home. But we're expecting a tougher match because they're the Six Nations champions who can run the ball and score tries. We're ready and up for the challenge."