Gayle is considered the most dangerous cricketer in the world. He underlined his supremacy last month with an astonishing innings of 175 not out for Royal Challengers Bangalore (RCB) in the Indian Premier League (IPL).
The South African captain also singled out Indian captain MS Dhoni, who has produced impressive scores in the IPL as skipper of tournament leaders Chennai Super Kings.
"The nature of ODI cricket is such that any player can take the game away on the day," said De Villiers, whose country has not won the Champions Trophy since 1998.
"I think looking specifically at our group, Chris Gayle is one of the major players that stands out, as well as Dhoni who is a master-class with the bat."
South Africa is in Group B alongside world champions India, current ICC World Twenty20 holders West Indies and Pakistan.
Australia, England, New Zealand and Sri Lanka make up group A.
The ICC Champions Trophy runs June 6-23 in England and Wales.