Schalke, who face Valencia in the Champions League round of 16 later this month, are 11th in the league, 25 points off Ruhr valley rivals Dortmund, who top the table with 16 wins from 20 matches.
Schalke coach Felix Magath has been in the firing line after a string of signings in the winter transfer window that have angered fans.
Two of the new recruits include 32-year-old Iranian Ali Karimi and 30-year-old Greek striker Angelos Charisteas, who was without a club since November.
Many Schalke fans, furious that Magath's 40 signings in 18 months have failed to deliver, are already calling it a "senior citizen team" but Klopp is wary.
"There are many advantages for Schalke in this game," Klopp warned ahead of Friday's clash in Dortmund.
"It is easier if there is quality in a team - and Schalke clearly have that - to turn a situation around and despite negative expectations to spring a surprise," he told reporters.
"In Germany this is the mother of all matches. We understand that the atmosphere is not particularly good (at Schalke) at the moment."
"But our plan is to stop the quality our rivals have from unfolding in the game," said Klopp.
Dortmund, who beat Schalke 3-1 in September, have not won both derbies in one season since their Champions League-winning 1996/97 campaign.
Klopp will have to make changes in central defence with Felipe Santana, who is yet to start this season, coming in to replace suspended Neven Subotic while Mario Goetze will again start in his offensive midfield role.
A defeat, however, is unlikely to rattle Dortmund, who are 11 points ahead of second-placed Bayer Leverkusen and 14 above champions Bayern Munich.
Schalke, though, are in desperate search of points as the battle for a European spots intensifies and a slip-up is likely to pile more pressure on Magath.
"Now we have a structure we can work with," said the 57-year-old of his new signings. One of them, Ghana international Anthony Annan, could make his first start on Friday.
Bayer Leverkusen, in improving form following the return of Michael Ballack, travel to Nuremberg while Bayern Munich take on struggling Cologne.
At the other end of the table Borussia Moenchengladbach could lift themselves off the bottom spot for the first time in months with victory over VfB Stuttgart, in 17th place and level on points with their opponents.
