The 43-year-old actor is not allowed to talk about his role as the baddie in the web-slinging comic book adventure, but said he’s "very, very excited about it.
"It’s a great script, great director and the money ain’t bad," he said.
Ifans may be best known for playing as Hugh Grant’s oddball roommate in 1999′s "Notting Hill." Recent credits include "Pirate Radio" and "Greenberg" opposite Ben Stiller.
Ifans will be starring opposite American-born and British-raised Andrew Garfield, who is taking over as Peter Parker.
"It is quite cool this one, to have Spider-Man and his villain both from the U.K.," Ifans said.
Filming is expected to star in December for a July 3, 2012 release. To be directed by Marc Webb, the film also stars Emma Stone as Gwen Stacy.