Caelan Doris captains a Leinster team that shows six changes to the matchday squad from last weekend's Investec Champions Cup final defeat. Get your tickets here.
This is Leinster's 11th successive appearance in the URC play-offs, winning all five of their quarter-finals to date, which have been played at three different venues in Dublin.
Leo Cullen's men ran out 31-7 winners when they hosted the Lions three weeks ago. Their only loss in their last five league matches was 29-26 away to Benetton.
Ireland winger James Lowe comes back into the starting XV to make his 100th appearance. He equalled Shane Horgan's all-time try-scoring record of 69 tries when he scored against the Ospreys.
Jimmy O'Brien replaces Tommy O'Brien on the right wing, while Rieko Ioane moves infield to reunite with Jamie Osborne in the same centre pairing from the round 17 victory over the Lions.
Full-back Hugo Keenan backs up for his seventh start since returning from injury in March. Sam Prendergast and Luke McGrath slot in as the starting half-backs.
Tadhg Furlong is bumped up from the bench to rejoin Andrew Porter and Dan Sheehan in a front row that boasts 401 Leinster appearances between the trio.
Joe McCarthy, who has scored four tries in his last two games, and James Ryan continue together in the engine room, with the last two changes in the back row.
Max Deegan, a second half replacement in Bilbao, and Scott Penny will join forces with Doris in the loose forwards. Josh van der Flier is set for a bench role.
Four more of the province's starters against Bordeaux-Bègles, Thomas Clarkson, Jamison Gibson-Park, Harry Byrne, and Robbie Henshaw, are selected as replacements this time.
While Paddy McCarthy will unfortunately miss the rest of the season with a foot injury, fellow loosehead Alex Usanov returns to complete the forward reinforcements alongside Gus McCarthy and Diarmuid Mangan.
As Leinster look to bounce back from their Champions Cup disappointment and successfully defend their URC title, Porter said: "We're lucky that we still have something to play for.
"We're throwing everything into it, into this weekend. And there's still a trophy to be won. We're leaving no stone unturned this week.
"We know it'll be a tough game against the Lions, but we're ready to flip the page and we're getting excited about it already.
"We can't reflect too long (on the Bordeaux game) and feel sorry for ourselves. You have to turn the page and switch the mindset onto the next game.
"We know from last year how that win at the end of the season kind of put a bit of a brighter shade on the end of the year."
LEINSTER (v Fidelty SecureDrive Lions): Hugo Keenan; Jimmy O'Brien, Rieko Ioane, Jamie Osborne, James Lowe; Sam Prendergast, Luke McGrath; Dan Sheehan, Tadhg Furlong, Joe McCarthy, James Ryan, Max Deegan, Scott Penny, Caelan Doris (capt).
Replacements: Gus McCarthy, Alex Usanov, Thomas Clarkson, Diarmuid Mangan, Josh van der Flier, Jamison Gibson-Park, Harry Byrne, Robbie Henshaw.