The pair worked together on the first instalment of the franchise in 2004, followed by the sequel in 2008.
"I can say publicly that now we are together in trying [to do Hellboy 3]," del Toro revealed to Entertainment Weekly at Comic-Con.
Perlman added: "The [first] two movies were really set up to have this unbelievable resolve. Everything that was done in both movies was leading up to this destiny, written in stone, of what Hellboy has been summoned to Earth to do.
"To not do it, particularly in light of the scope that Guillermo is thinking of for the resolve, would be in my mind a little bit of a shame."
Earlier this month, Perlman donned his superhero costume with full make-up to spend a day with a 6-year-old boy as part of his Make-a-Wish Foundation request.
Perlman and del Toro have teamed up again for new movie Pacific Rim, about a war between mankind and monsters called Kaiju.
The film will open to cinemas on July 12, 2013.
Watch the trailer for Hellboy II: The Golden Army below: