The award-winning stage show is running at the Apollo Theatre in London's West End.
The comedy stars will be joining the cast this March, with Hound set to play Hugo/Loco Chanelle, and Brand as Miss Hedge.
Katy Brand says: "Joining the cast of Everybody's Talking About Jamie is a truly thrilling opportunity for me. If I could tell my teenage self that I would one day have the chance to perform in a huge hit show on the West End stage, that girl would pinch herself. Jamie gets to realise his dream every night, and now so do I!"
Rufus Hound comments: "I'm absolutely thrilled to be going into the cast of Everybody's Talking About Jamie - a brilliant, brave and British smash hit. I have been waxing for the last year in anticipation and am currently so tucked I may as well be a Ken doll. Bring. It. On."
Producer Nica Burns says: "We are delighted that Katy Brand will be joining the cast as Miss Hedge and Rufus Hound as Hugo/Loco Chanelle. They will both bring their own incredible talent to their roles and make them their own."
Everybody's Talking About Jamie focuses on a sixteen year-old boy who lives in Sheffield. The plot is described as: "Supported by his brilliant loving mum and surrounded by his friends, Jamie overcomes prejudice, beats the bullies and steps out of the darkness, into the spotlight."
The duo will join the current cast, which is lead by Noah Thomas in the role of Jamie New.
Katy Brand will play Miss Hedge from 3 March until 20 June 2020 and Rufus Hound will play Hugo/Loco Chanelle from 16 March until 30 May 2020. Tickets are available via everybodystalkingaboutjamie.co.uk
For updates, click the buttons below.