The Championship club will need to find around £40m to comply with Financial Fair Play regulations.
Grealish has been an asset to Villa, scoring nine goals in 92 league games.
Steve Bruce told 'Sky Sports': "He's a special talent. Yes, you don't want to lose him, but the inevitable thing is, we have to."
"We have to to keep the club up and running and keep it in line with Financial Fair Play."
"We might have to take decisions which aren't going to be easy. We will have to generate some money and inevitably that's going to be through player sales," he added.
"And it's going to be people who I don't want to sell. The obvious one is Jack. People will know we've got financial problems and they'll sit and wait until deadline day possibly, I hope that doesn't happen but we've got to wait for it."
The former England Under-21 player has been linked to a move to Premier League club Tottenham.