Anderlecht overcame Villarreal in the previous round, while AZ Alkmaar dispatched Lazio to book their place in the last eight.
Match preview
It would not be unfair to say that Anderlecht have experienced a turbulent Europa Conference League campaign up to now, recording four wins, three draws and three losses since the start of the competition.
After taking eight points from a possible 18 during the group stage - finishing 10 points behind West Ham United in Group B - Brian Riemer's side required penalties to get past Ludogorets Razgrad in the first knockout round.
Given their inconsistency in Europe, Anderlecht were not expected to overcome Villarreal in the last 16, but the Belgians managed to hold the Spaniards to a 1-1 draw in the first leg before clinching a famous 1-0 victory at El Madrigal.
Thanks to those results, RSCA head into Thursday's clash on a six-game unbeaten run across all competitions, having picked up four wins and two draws since their last loss while keeping a clean sheet in each of their previous five outings.
Having suffered a solitary defeat in their last 10 matches - losing just two of their previous 15 encounters in all competitions - Anderlecht will be confident of notching a first-leg advantage on home soil.
Meanwhile, AZ Alkmaar had to come through three qualifying rounds to reach the Europa Conference League, dispatching Tuzla City, Dundee United and Gil Vicente to punch their ticket to the competition proper.
The Cheeseheads ended up making light work of their group-stage opponents, however, finishing five points clear at the top of Group E after winning five of their six matches to earn a direct route to the round of 16.
AZ headed into their last-16 clash with Lazio as underdogs, but they managed to claim a couple of 2-1 victories over the Italian club, coming from behind in both games while showing off their fighting spirit.
That said, Pascal Jansen's side have failed to taste victory since overcoming Lazio, taking one point from a possible nine to leave them fourth in the Eredivisie table - five points shy of the European places and 13 points behind table-topping Feyenoord.
AZ enjoyed an eight-game unbeaten run between November and February before racking up five straight wins across February and March, but Jansen's men have endured a noticeable drop-off in recent weeks.
Anderlecht Europa Conference League form:
D
W
L
W
D
W
Anderlecht form (all competitions):
D
W
W
W
W
D
AZ Alkmaar Europa Conference League form:
W
L
W
W
W
W
AZ Alkmaar form (all competitions):
W
W
W
L
D
L
Team News
Anderlecht will be without Yari Verschaeren for the remainder of the campaign after the 21-year-old playmaker sustained an ACL tear last month, while Adrien Trebel is also out injured.
Verschaeren bagged two goals and two assists in the Europa Conference League before getting injured, so Islam Slimani - who has scored seven goals in 12 games since arriving in January - must continue to find the back of the net.
At the opposite end of the pitch, goalkeeper Bart Verbruggen will aim to keep a sixth successive clean sheet on Thursday, with the help of veteran centre-back Jan Vertonghen.
AZ Alkmaar look set to be without Jesper Karlsson for the first leg after the Swedish forward missed last weekend's 1-0 defeat to Sparta Rotterdam due to a muscle injury.
There are also question marks over the fitness of Maxim Dekker, Bruno Martins Indi, Sem Westerveld and Dani de Wit, who have all missed recent matches through injury.
Greek striker Vangelis Pavlidis has chalked up 19 goals and 10 assists this season and scored in both games against Lazio, while versatile Danish forward Jens Odgaard has contributed 11 goals and five assists.
Anderlecht possible starting lineup:
Verbruggen; Murillo, Debast, Vertonghen, N'Daiye; Ashimeru, Diawara, Arnstad; Dreyer, Slimani, Amuzu
AZ Alkmaar possible starting lineup:
Ryan; Sugawara, Beukema, Hatzidiakos, Kerkez; Reijnders, Clasie; Odgaard, Mijnans, Mihailovic; Pavlidis
We say: Anderlecht 1-0 AZ Alkmaar
While AZ Alkmaar have failed to win any of their last three games, Anderlecht have won four of their previous five, keeping five clean sheets in the process.