Nacer Chadli, Mousa Dembele and Jan Vertonghen are in the Belgium squad while Ben Davies is in the Wales corner for the Group B encounter at the King Baudouin Stadium.
Wales currently top the group with two wins and a draw from three matches while pre-group favourites Belgium have four points out of six.
Wales are chasing their first appearance in a major tournament finals since 1958 and with a change in qualifying - the top two from each group and the team with the best record in third place will progress to the finals in France, the remaining third-placed teams go into a play-off - they appear to have their best chance in years.
So it's a huge game - and we spoke to all four of our players about it before they left Hotspur Way to hook up with their national squads.
Belgium are favourites to qualify and Wales are now serious competitors, especially with how they've started the group and the new qualification processs. How important is this game?
Nacer: "It’s an important game. We’ve started well in the campaign and now we play Wales, a strong side with quality players but I believe we also have the quality to take the three points at home. I hope we get the win and we get to the European Championships."
Mousa: "Wales have some quality players like Ben, Bale, Ramsey, Allen and Williams, so we know we have to be careful. Everyone knows we have good players as well and we play at home, so it’s a game we have to win."
Ben: "These are big games for us. Maybe in the past we wouldn’t have been expecting to take points in them but we’re going into these games looking to pick up points. If we manage to take anything from them, especially away from home, it would be great and with players like Gareth Bale in the team, you know you have a chance."
Jan: "Wales are a very good team with very good players, we knew that before anyway. Okay, they are not a name like Germany or France but if you see their players, they are all in the Premier League. They have strength in every position. We will be happy if we win this game."
How strange is it when you play against club team-mate in an international?
Mousa: "I think we’re used to it now, we’ve played internationals for a few years, so it’s not that strange anymore."
Jan: "It’s funny. The banter is always there when you play against your team-mates. We played against Nabil in the World Cup. I’m looking forward to it because it’s always special."
Ben: "It’s quite strange but it’s one of those things where for the 90 minutes on the field you have to forget they are team-mates and they are opponents. It’s a game we will go 100 per cent for and I’ll be ready, whoever I’m playing against. We’ve had a laugh and a joke about it but I’m not sure the Belgians are quite as confident now!"
Wales haven't qualified for a major tournament since 1958. Belgium qualified for their first World Cup finals in 12 years this time around in Brazil. So Nacer, how much did it mean to qualify for the World Cup and Ben, what would it mean to get to Euro 2016?
Nacer: "It meant a lot. Belgium didn’t qualify for a long time but we qualified for the World Cup and it was amazing to experience that with the guys. Now we want to do everything we can to make it to the European Championships and we know we have a strong team to do it, we just have to focus."
Ben: "It would be huge if we could make it into the finals of a major tournament. It would mean so much to everyone as players and as a nation. It would be unbelievable."