The fourth biennial fundraiser will also feature Pierce Brosnan, Jennifer Aniston, Halle Berry, Jon Hamm, Will Ferrell and Ncis star Mark Harmon, while The Who, Jennifer Hudson, Lupe Fiasco & Common, Ariana Grande and Dave Matthews will perform.
Paltrow, who lost her father Bruce to oral cancer in 2002, will also co-executive produce the broadcast live from the Dolby Theatre in Los Angeles.
She says, "Cancer affects us all and each and every person can help the scientists who are working 24/7 to save more lives.
"We want to get that message out in as many ways as possible, so we're excited to use social media to reach supporters from all over who are helping to grow the Stand Up To Cancer movement, and hopefully, get even more people to stand up with us."
For the first time, a 'digital lounge' will replace the traditional phone bank staffed by celebrities, and from there celebrities will be able to reach out to viewers via phone, Facebook, Instagram and other social media platforms.
The Su2C initiative launched in 2008, and telethons have been held in 2010 and 2012. They have raised a total of more than $260 million (Gbp153 million) for cancer research charities.