The dance and entertainment entrepreneur, who was fired during last week's semi-final, argued that the BBC business contest could survive without Lord Sugar in charge.
Speaking to DS at the Big Talent Group summer party in Mayfair last night (July 16), MacDuff-Varley stated: "I think that Lord Sugar is really integral to it, but I think someone on that same level as him... could actually do it.
"The Apprentice is an amazing programme in its own right. It would be very hard to replace him, but who knows... I think the obvious choice to step in would be Karren Brady.
"She's been there all along, she's successful, she runs businesses and she's a fierce lady. Karren stepping up would be great, but I don't think she'd do that out of respect for Lord Sugar."
MacDuff-Varley also commented on photos of her dining out with former Apprentice winner Stella English, dismissing suggestions that their friendship could hurt her chances of doing business with Lord Sugar after English unsuccessfully sued him for constructive dismissal.
"When you've been compared to someone for three months you've got that natural curiosity to see what the person is like," she said. "There was nothing in it. We went for lunch and someone thought it was newsworthy.
"I think she's lovely and whatever's gone on with her and Lord Sugar is between them. I think that Lord Sugar is very respectful and an integral man. I don't think he judges people like that. I don't think he's petty or like a schoolchild or anything.
"I've never been told who I can and can't like and if I want to make my own decisions about people I will do, and I think Lord Sugar respects that."
MacDuff-Varley is returning to The Apprentice for tonight's (July 17) final, where she will help Leah Totton launch her medical cosmetic business in an effort to beat Luisa Zissman to Lord Sugar's £250,000 investment.
Asked if she thought the boss would ever partake in Totton's treatments, MacDuff-Varley replied: "I can't see Lord Sugar ever giving [Botox] a go, but you never know, he might try some other things."
The Apprentice concludes at 8pm on BBC One.