Vo filme Horton hrajú Jim Carrey (Horton (voice)), Steve Carell (Mayor (voice)), Carol Burnett (Kangaroo (voice)), Will Arnett (Vlad (voice)), Seth Rogen (Morton (voice)), Dan Fogler (Councilman / Yummo Wickersham (voice)), Isla Fisherová (Dr. Mary Lou Larue (voice)), Jonah Hill (Tommy (voice)), Amy Poehler (Sally O'Malley (voice)), Jaime Pressly (Mrs. Quilligan (voice)), Charles Osgood (Narrator (voice)), Josh Flitter (Rudy (voice)), Niecy Nash-Betts (Miss Yelp (voice)), Jesse McCartney (JoJo (voice)), Shelby Adamowsky (Hedy / Hooly (voice)), Jack Angel (Old Time Who (voice)), Caitlin Rose Anderson (Helen (voice)), Emily Anderson (Heather (voice)), Jan Rabson (Town Cryer (voice)), John Cygan (Who (voice)), Jess Harnell (Another Who (voice)), Debi Derryberry (Who Mom (voice)), Samantha Droke (Hildy / Holly (voice)), Karen Disher (Who Kid (voice)), Marshall Efron (Wickersham Guard 1 (voice)), Bill Farmer (Willie Bear (voice)), Jason Fricchione (Joe (voice)), Heather Goldenhersh (Who Girl (voice)), Selena Gomez (Helga (voice)), Jimmy Hayward (Obnoxious Who (voice)), Joey King (Katie (voice)), Christina Martino (Heidi / Haley (voice)), Ellie Martino (Hanna (voice)), Laraine Newman (Glummox Mom (voice)), Tim Nordquist (Wickersham Guard 2 (voice)), Colleen O'Shaughnessey (Angela (voice)), Laura Ortiz (Jessica (voice)), Joe Pasquale (The Dentist (voice)), Connor Anderson (Who Child #1 (voice)), Isabella Acres (Additional Voices (voice)), Bob Bergen (Additional Voices (voice)), Jeff Biancalana (Additional Voices (voice)), Madison Davenport (Additional Voices (voice)), Teresa Ganzel (Additional Voices (voice)), Kathy Graves Toon (Additional Voice (voice)), Sherry Lynn (Additional Voices (voice)), Danny Mann (Additional Voices (voice)), Mona Marshall (Additional Voices (voice)), Mickie McGowan (Additional Voices (voice)), Madison Pettis (Additional Voices (voice)), Grace Rolek (Additional Voices (voice)), Jennessa Rose (Additional Voices (voice)), Ariel Winter (Additional Voices (voice)), Fletcher Sheridan (Jojo (singing voice) (uncredited)).