The writer and artist made it "very clear" that there would not be a third movie based on his Dark Horse Comics title during his San Diego Comic-Con International panel, according to Comic Book Resources.
Hellboy director Guillermo del Toro and star Ron Perlman had previously said at Comic-Con that they are trying to make a follow-up to the 2004 film and its 2008 sequel.
"I can say publicly that now we are together in trying [to do Hellboy 3]," del Toro told Entertainment Weekly.
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."
Mignola also discussed the Hellboy comic and its B.P.R.D. spinoff.
"Things are building to some really gigantic stuff by the end of the year," he said of the latter, which has received numerous miniseries in 2012.
He said that his character's return in the four-issue Hellboy in Hell miniseries would be followed by series of one-shots and two-part stories.
Mignola also revealed plans to adopt a sequential numbering system for future Hellboy comics to make the storylines easier to follow.
Hellboy in Hell #1 will be released on December 5.
Watch the trailer for Hellboy II: The Golden Army below: