The hosts are still yet to be beaten in any competitive match this season, while the visitors will be looking to end that fantastic streak and secure their place in the final.
Match preview
Xabi Alonso's men have been simply superb throughout this season, playing 39 times across all competitions and, remarkably, they are still yet to be beaten in that period.
Leverkusen have come close to defeat multiple times in the past few weeks, but they have been able to fight back late on in every game to keep the streak going, serving as a testament to the side's resilience.
The latest of those came in the Bundesliga leader's previous outing against Hoffenheim which saw them enter into the final minutes of the match trailing 1-0, but two goals from Robert Andrich and Patrik Schick in the dying moments saw Alonso's side turn the game on its head and come out with a thrilling victory.
With the Bundesliga title looking certain to be theirs, and already securing their place in the UEFA Europa League quarter-finals, thanks to yet another last-gasp winning moment from Schick, Leverkusen could still be on to complete a fantastic treble come the end of the season.
Die Werkself are heading into this tie as the strong favourites to secure yet another victory, but the DFB Pokal has provided plenty of major upsets this season, with none bigger than the defeat of Bayern Munich by fellow semi-finalists Saarbrucken, leaving no room for complacency in this one.
While Dusseldorf will understand the magnitude of the task at hand, they will be relying on yet another David versus Goliath scenario in this semi-final.
If they are able to pull off that unlikely feat then Daniel Thioune's side would be looking at an all-lower division final, with the first of the two semi-finals seeing 3. Liga Saarbrucken take on second-tier Kaiserslautern.
The visitors have been enjoying a good season in the 2. Bundesliga, currently residing in third place and still in the hunt for an automatic promotion spot to get themselves back in the top flight for the first time since the 2019-20 season.
Their away form has been their strength in the league, winning seven and drawing four of their 14 meetings on the road, but travelling to the BayArena will provide a much tougher challenge than they are currently used to.
Dusseldorf have not beaten Leverkusen since a 1-0 victory in 1996, and they will now be hoping their on-loan talisman Christos Tzolis, who has scored 19 goals this campaign, can help them to not only their first victory over the hosts in 18 years but also secure a historic place in the final of this competition.
Bayer Leverkusen DFB-Pokal form:
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Bayer Leverkusen form (all competitions):
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Fortuna Dusseldorf DFB-Pokal form:
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Fortuna Dusseldorf form (all competitions):
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Team News
Alonso will have to deal with three injuries to his squad for this upcoming semi-final, with Arthur and Victor Boniface both extending their lengthy spells on the treatment table.
Exequiel Palacios is the other player who will be missing for this match after the midfielder suffered a hamstring injury earlier this month.
As for Thioune's side, they will also be without multiple players ahead of this fixture.
Daniel Bunk and Nicolas Gavory are not expected to return to action until late April, but Marcel Sobottka (illness) and Takashi Uchino (head injury) could return for this one.
Bayer Leverkusen possible starting lineup:
Kovar; Tapsoba, Tah, Hincapie; Frimpong, Andrich, Xhaka, Grimaldo; Hofmann, Wirtz; Schick
Fortuna Dusseldorf possible starting lineup:
Kastenmeier; Zimmermann, Oberdorf, Siebert, Uchino; Engelhardt, Tanaka; Klaus, Appelkamp, Tzolis; Mustapha