This clash pits the sides second from top and second from bottom against one another.
Match preview
To the naked eye, Galatasaray have been in imperious form, and the results agree with that, but their actual performances have been very up and down despite winning six and drawing one of their last seven games.
This will be their first league match since their astonishing 7-0 demolition away at Istanbul Basaksehir before the World Cup break, a result which will go down as one of the most extraordinary across Europe this season.
That was their second 7-0 win in the space of a month having dished out similar treatment to Kastamonuspor in the Turkish Cup.
However, in the next round of the cup, they had to come from behind with a late winner to see off Ofspor - a side sat far adrift at the bottom in the fourth tier.
Their return to competitive action saw them edge past Keciorengucu in the fifth round on Thursday too, with a late Bafetimbi Gomis winner needed to seal a 1-0 victory.
Despite that though, Okan Buruk's side are in a very healthy position on the league front, closing the gap to just two points on leaders Fenerbahce with that win over Basaksehir, taking advantage of their rivals slipping up against Giresunspor.
For Istanbulspor, the games just continue to get tougher.
In their first competitive game back after the break they faced Fenerbahce away from home in the cup, and unsurprisingly lost 3-1.
Now they lock horns with another local giant, and the second best side in Turkey at the moment.
Having lost their final six league games before the mid-season break, this is not the match they would have wanted to restart with to try to get their season back on track.
Manager Fatih Tekke is yet to pick up a point as manager and also lost 4-0 to Besiktas in their only friendly during the intermission.
Things have only got worse since he arrived for a third spell in charge, with Istanbul's fourth club sitting second from bottom, five points from safety, as having the second-worst attack and second-worst defence has now caught up with them following a respectable start.
They may be relatively thankful that this is an away fixture though, as Istanbulspor have one of the worst home records in Europe, having picked up just one point from a possible 18 in the league so far this season.
Galatasaray Turkish Super Lig form:
D
L
D
W
W
W
Galatasaray form (all competitions):
W
W
L
D
L
W
Istanbulspor Turkish Super Lig form:
L
L
L
L
L
L
Team News
Kerem Akturkoglu has become undroppable despite all the star names in the Galatasaray squad, thanks to his hattrick against Basaksehir in their last league outing.
Mauro Icardi and Sergio Oliveira were given extended time off during the World Cup and it is unclear whether they will feature here having neither played any part in the cup win on Thursday.
Emre Tasdemir went off injured in the win over Basaksehir and has not played since, so either the experience of Patrick van Aanholt or the youthful Kazimcan Karatas will be utilised at left-back.
Yusuf Demir is fit again having not featured at all through October and November, but Mathias Ross remains out injured.
There are no new injury concerns for Istanbulspor, and Tekke named a full strength side for the cup defeat at Fenerbahce.
Many of the same starters from the loss to Hatayspor before the break were in from the outset on Tuesday so they could remain largely unchanged.
Adi Mehremic is back from suspension after being sent off against Giresunspor so should return to the back four, but fellow Bosnian Denis Kovacevic is still yet to make his debut since arriving from Zeljeznicar.
Galatasaray possible starting lineup:
Muslera; Boey, Nelsson, Bardakci, Van Aanholt; Torreira, Midtsjo, Rashica, Mertens, Akturkoglu; Seferovic
Istanbulspor possible starting lineup:
Jensen; Berber, Yesil, Mehremic, Yasar; Sarikaya, Kabasakal, Rroca, Topalli, Ethemi; I Yilmaz
We say: Galatasaray 3-0 Istanbulspor
Galatasaray are either clinical or unconvincing at the moment, but always seem to get the win, and a struggling Istanbulspor low on confidence will likely have no answer to their firepower.