Regular Hurricanes captain Matthew Wade will miss the match at Blundstone Arena after being suspended for incurring his third code of conduct breach within 18 months.
The charges in that period relate to two instances of use of an audible obscenity and one instance of abuse of cricket equipment.
Paine will don the gloves for Hobart in his first BBL match since February 2018.
Top-order batter Ben McDermott is out with a hamstring niggle, replaced by Caleb Jewell.
The unbeaten Renegades, who will go to the top of the table with a win, have made one change to their XI with David Moody coming in for Kane Richardson (rested).
Hobart Hurricanes: Nathan Ellis (capt), Asif Ali, Tim David, Patrick Dooley, Caleb Jewell, Shadab Khan, Riley Meredith, Jimmy Neesham, Tim Paine, Joel Paris, D'Arcy Short.
Melbourne Renegades: Nic Maddinson (capt), Aaron Finch, Jake Fraser-McGurk, Sam Harper, Akeal Hosein, David Moody, Tom Rogers, Andre Russell, Will Sutherland, Mujeeb Ur Rahman, Jono Wells.
