Etheridge will make her third appearance on the show, to be broadcast Wednesday at 8 p.m., The New York Daily News reported.
The show has been credited with finding homes for 20,000 children.
"You just can't beat it for the feeling of the season, or what this season is about," Etheridge said. "This is about understanding, giving, gratitude and hope and this show puts children into families and homes."
Other guests on the show include Katy Perry, Ricky Martin, Maroon 5, Nelly and Sharon Osbourne.
The concept for the show was created 13 years ago; this is its 12th year on CBS.
Jack Sussman, executive vice president of specials, music and live events for CBS, said if the show finds a home for one child it will be a hit.
"The message is, we have an ability to do something about children who don't have a home," Sussman said.
Sussman said putting a special together can be difficult; he said the key is to get a wide variety of artists whose mere presence will get some people to watch, and perhaps think about adoption in ways they normally wouldn't.
In one segment, country singer Jimmy Wayne talks about his experience about being abandoned at a bus station when he was 13, and his journey through eight foster-care homes before finding a couple in their 70s who gave him a home.
"I know these producers," Etheridge said. "They know how to make it entertaining and uplifting. They'll tug at your heartstrings but not lay you out on the floor."