The Spain and Real Madrid custodian has questioned the big-match temperament of Robert Green, David James and Joe Hart ahead of the tournament, which gets under way on Friday.
None of the England goalkeeping trio featured for their club sides in Europe last season, while both Portsmouth's James and Green of West Ham lined up for teams battling relegation from the Barclays Premier League.
Casillas, a key member of Spain's Euro 2008-winning squad, believes top teams will be able to expose England's frailties in that area.
He said: "I can see why both Lionel Messi and Xavi have talked up England's chances at the World Cup because their class is undisputed. But their goalkeeping situation is a real problem.
"None of the keepers have played even European Cup level, that's the highest level you can play at club level.
"And if you have never played in the top club competition in the world, you are going to find it hard to perform at the top international level in the world when even more eyes are on you.
"If you look at myself, Gigi Buffon of Italy and Julio Cesar of Brazil, we are keepers who've all won European Championships, World Cups and European Cups.
"At this level nerves play a big part and any mistake a goalkeeper makes is going to be scrutinised.
"It's not always about ability at the World Cup, it's about having been there before and knowing how to handle the big games."
England coach Fabio Capello has left England's fans guessing as to who his first-choice goalkeeper will be in South Africa, but Casillas believes he knows who will get the nod.
"I don't see that England coach Fabio Capello has any choice but to play Robert Green," he added.
"It doesn't matter if Joe Hart has more natural ability. To throw him into the World Cup with no experience would be crazy and Fabio is far more intelligent than that. He has stuck with Robert Green throughout the qualifying stages and that is the way I am sure it will stay."
Despite his obvious reservations about the England squad, Casillas added: "Apart from the keeper situation, England are very strong and I'd put them in the top three favourites, along with us and Brazil."
Meanwhile, Sven-Goran Eriksson believes England can win the World Cup despite the setback of losing captain Rio Ferdinand.
The former England manager, now in charge of the Ivory Coast, has his own problems with Didier Drogba undergoing an operation after breaking an arm. But he is still hopeful his side can set up a potential semi-final with England.
Eriksson said: "If they (England) don't have more bad luck with injuries they have a chance to go the whole way and I would be happy for them if that happens.
"I think they have a good chance. I hope for their sake that Wayne Rooney will stay fit for the tournament. I think he is extremely important for England as Drogba is for us."
When asked would England reach the final of the World Cup, he replied: "Yeah, why not, or the semi-final against the Ivory Coast."
On Ferdinand's injury, he said: "It's sad news. Rio Ferdinand is one of the best defenders in the world. Bad news for England and bad news for the World Cup.
"But England have a lot of other good footballers in their squad, especially if you talk about midfielders and defenders."