Having struggled during the first half of the Bundesliga season, Jurgen Klopp's side have lifted themselves away from relegation trouble with three successive league victories.
They sit three points above the danger zone in 12th, but face a tough test to make it four triumphs in a row this weekend.
Matches between the two sides are one of the spectacles within the German top-flight season, although both clubs will be hoping no trouble erupts as it did in 2013 when eight Dortmund fans were arrested.
Roberto Di Matteo's side have enjoyed much more success this season with 10 wins helping them into the top four, and in a battle for the final automatic UEFA Champions League spot.
"Dortmund are a top team that has had a difficult period," Schalke defender Benedikt Howedes told Kicker. "As it is, they have recovered from it and play really good football again.
"But we do not want to be the opponent who continues to allow Dortmund to build. We need the three points."
Schalke will welcome back Klaas-Jan Huntelaar after his domestic suspension, while the hosts are sweating on the fitness of Neven Subotic and Kevin Kampl, who missed Tuesday's Champions League defeat to Juventus through illness.
Hamburg are another side seeking to pull away from danger and they travel to Eintracht Frankfurt, who sit four points above them.
With only seven points covering the bottom half of the table, the teams in the relegation places have not given up hope of escaping.
Hertha Berlin, who have just one win in seven, welcome an out-of-sorts Augsburg to the Olympiastadion, with the visitors having failed to win any of their last three matches in the league.
Just above Hertha are Freiburg, but their chances of moving out of the relegation play-off place look slim ahead of a trip to Bayer Leverkusen, although the strugglers will hope Roger Schmidt's will suffer from a European hangover.
Bottom club Stuttgart need a victory to avoid being cut off at the bottom, and they face another side in poor form in Hannover, while Mainz visit Hoffenheim.
Meanwhile, league leaders Bayern Munich will look to extend their eight-point advantage with a home clash against Cologne on Friday, with Pep Guardiola's side unbeaten at the Allianz Arena since April 2014.
Worryingly for Cologne, Bayern have been in ruthless form in the league since their wobble after the mid-season break, scoring 16 goals without reply in their last three matches.
Second-placed Wolfsburg travel to Werder Bremen as they try to hold onto Bayern's coat tails, while Borussia Monchengladbach's promising campaign takes them to Paderborn.
