The meeting will be the side's second in the week, following Tuesday's Pokal quarter-final, which Dortmund won 1-0 thanks to Pierre-Emerick Aubameyang's 83rd-minute strike.
After a strong start to the season, Jurgen Klopp's side have suffered a woeful downturn in form, a run of three wins from their last nine games has left them 17 points adrift of league leaders Bayern Munich.
With their chances of the title all but gone, Dortmund's main focus may switch to the Pokal and UEFA Champions League.
Having made last season's Champions League final, only to be beaten by Bayern, Dortmund's quest to reach the showpiece again will continue with a round-of-16 tie against Zenit St Petersburg - the first leg of which takes place on February 25.
They cannot afford to become sidetracked though, with Schalke and Borussia Monchengladbach breathing down their necks in search of the third and final automatic Champions League qualification berth.
Saturday provides Dortmund an opportunity to improve their recent wretched home form, with just one point taken from their past four matches at Signal Iduna Park.
Frankfurt have suffered a similarly miserable run on their travels, with just one win on the road in the last seven league games, although that did come at second-placed Bayer Leverkusen back in December.
Sven Bender and Marco Reus are doubts for the game with thigh injuries, although Klopp hinted on Thursday that they could be involved.
Tuesday's match-winner Aubameyang, meanwhile, believes the side can clinch silverware this season as long as the players fight hard for each other.
"There's a lot of quality in the squad," he said.
"We can achieve much more if we stick together. If we play with a knife between our teeth and fight until we drop we can go far in every competition."
Frankfurt finished sixth last season, earning a spot in the UEFA Europa League, though the added commitments may have hindered them and they are currently 12th, only four points off the relegation play-off spot.
Their task against Dortmund will not be made any easier by the loss of captain Pirmin Schwegler, who suffered cracked ribs in last weekend's win over Eintracht Braunschweig.
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