The South African is partnered at halfback with Ian Humphreys, and the back-line remains otherwise unchanged.
Paddy McAllister has also been given an opportunity to start at loosehead prop, with Ireland international Tom Court making way.
Stefan Terblanche, who arrived in Belfast last Sunday, has gone straight into the matchday squad and will win his first cap for the province if he is used as a replacement.
The former South Africa international has the ability to cover full-back, wing and centre. Elsewhere on the bench, Andi Kyriacou will provide cover at hooker instead of Nigel Brady.
Commenting on his scrum half selection, Ulster head coach McLaughlin said: "Paul is a terrific player and has proved himself over the past few weeks.
"But Ruan was the league's Player of the Year last season so he deserves a chance. His game-time has been limited so it will be good for him to get some time on the pitch. We now have two quality scrum halves."
He continued: "It was important for Paddy McAllister's development to start in a match at this level. And it means we have the option to bring a quality player like Tom on if we need to.
"We also have Stefan in the squad. He's a true professional and will add a great deal to the team in terms of his experience. He's an international player and has played for the Ospreys in Europe so he will be comfortable if he comes on."
There are still tickets available for Friday's game. They can be bought online at www.ulsterrugby.com or by calling the ticket office on 02890493222 (ticketing option). Alternatively, you can pay at the gate on match night.
Fans should be aware that ticket zoning and scanning will be in operation at the ground. Supporters should check their tickets to ensure that they are entering through the correct gate. Further details are available here.
Ulster Rugby are advising supporters coming to the game (gates open 5.30pm) to avoid parking in the immediate vicinity of the Ravenhill grounds and that the following roads are only accessible for residents and closed to everyone else - Onslow Parade, Ravenhill Park and Ravenhill Park Gardens.
There will also be parking restrictions in place in the Castlereagh area (Mount Merrion Avenue). Supporters are encouraged to make use of the Park 'n' Ride facilities at Pirrie Park and along Montgomery Road.
ULSTER (v Aironi Rugby): Adam D'Arcy; Andrew Trimble, Darren Cave, Nevin Spence, Craig Gilroy; Ian Humphreys, Ruan Pienaar; Paddy McAllister, Rory Best, John Afoa, Johann Muller (capt), Dan Tuohy, Stephen Ferris, Chris Henry, Pedrie Wannenburg.
Replacements: Andi Kyriacou, Tom Court, Adam Macklin, Lewis Stevenson, Robbie Diack, Paul Marshall, Paddy Jackson, Stefan Terblanche.