The Vicky Cristina Barcelona star picked up the award for best film actress at the ceremony, which celebrates the achievements of Hispanic artists in film, television and music.
Hayek was given the Anthony Quinn Award for Industry Excellence, while family drama Nothing Like the Holidays, starring Debra Messing and John Leguizamo, took home three honours.
Make-up artist Jeanne Van Phue and hairstylist Mary Ann Valdes were honoured for their work behind the scenes of vampire movie Twilight.
Other winners on the night included The Office's Oscar Nunez, who was named best comedy actor, and Selena Gomez, who scooped best comedy actress for her part in the Disney Channel's Wizards of Waverly Place.
The ceremony was held at UCLA's Royce Hall in Los Angeles, and was hosted by George Lopez and Eva Longoria Parker.