The hosts currently sit in fifth spot in the Championship table due to two consecutive wins, while Wednesday fell to a disappointing defeat in a South Yorkshire derby against Rotherham United, moving them further from safety.
Reading secured another important win last time out, as George Puscas fired them to a 1-0 victory at home to Blackburn Rovers on Tuesday night.
That followed another 1-0 win, when Michael Morrison scored the only goal of the game in a victory away at Rotherham United.
Despite the good form of the teams below them, Veljko Paunovic's side have managed to keep hold of their spot in the playoffs thanks to those two recent wins, remaining three points ahead of seventh-placed Barnsley, who are in hot pursuit of the top six.
Paunovic will be hoping his side can record a third consecutive league win here as they look to fend off the likes of Barnsley and Cardiff City, as well as putting pressure on the sides above them, currently sitting just six points behind second-placed Brentford.
The Royals do boast a fairly strong record at home, having won 10 of their 17 league games on home turf this season, with only five sides picking up more than the 30 points they have accumulated at their Berkshire ground.
However, their opponents will not be a pushover on Saturday, as they take on a Sheffield Wednesday side who are fighting for survival and will be desperate for a result at the Madejski Stadium.
Last time out, Darren Moore's side travelled to Rotherham United in a crucial game at the bottom of the Championship table, as they looked to gain ground on the sides above them.
They did not get off to a good start though, as Michael Smith put the Millers ahead, before he was shown a red card and Matthew Olosunde turned the ball into his own net with 10 minutes to go, seeing the Owls go level with a one-man advantage.
However, it was their hosts who would get the winner, when Freddie Ladapo finished off a counter-attack in the 97th minute following a Sheffield Wednesday corner to snatch a 2-1 win.
That goal condemned the Owls to a fifth consecutive league loss, a run which has seen the South Yorkshire outfit fall seven points adrift of safety.
After the fourth defeat of that run, caretaker manager Neil Thompson was replaced by Darren Moore, as the Sheffield Wednesday hierarchy look to avoid relegation down to League One after seven seasons in the second tier.
However, that job is looking tougher every week as they now sit seven points behind Birmingham City, with Reading and league leaders Norwich City as their next two fixtures.
Worryingly for Moore, his new team currently have the one of the worst away records in the Championship, having picked up just 11 points from their 17 games on the road this season, an unconvincing sign as they look to overcome a six-point deduction and avoid the drop.
Reading Championship form: LWLLWW
Sheffield Wednesday Championship form: WLLLLL
Reading are expected to be without experienced centre-back Michael Morrison, who was forced off with an injury after half an hour in the recent win over Blackburn.
Midfielder Andy Rinomhota was absent from the squad in the Blackburn game, after he came off late in the win over Rotherham.
They also remain without influential midfielder John Swift, who has only featured in nine league games this campaign due to two separate spells out through injury, joining striker Yakou Meite on the sidelines.
George Puscas put forward his claim for another start with the winning goal against Blackburn, as Paunovic could continue with the system of two strikers with the Romanian partnering with the clinical Lucas Joao.
The Owls' injury list has continued to grow in recent weeks, while several key first-team players continue lengthy spells on the sidelines including midfielder Massimo Luongo and centre-back Dominic Iorfa.
Andre Green will also miss this game, with the January signing failing to hit the ground running in Sheffield having only made two appearances for the club due to an Achilles injury.
Elias Kachunga could come into the starting side for this game, adding some pace and creativity from the wing.
Reading possible starting lineup:
Cabral; Yiadom, McIntyre, Moore, Richards; Laurent, Semedo; Ejaria, Olise; Joao, Puscas
Sheffield Wednesday possible starting lineup:
Wildsmith; Palmer, Lees, Borner, Penney; Hutchinson, Shaw; Kachunga, Bannan, Windass; Paterson
We say: Reading 2-1 Sheffield Wednesday
While the Owls will be desperate for their first win under Darren Moore, we see them being outclassed by Reading who are determined to keep their place in the playoffs.
Their dangerous attacking players should create plenty of problems for a Wednesday defence that has been struck by injuries, and we predict a third consecutive victory for the Royals here.