Both sides find themselves in trouble at the wrong end of the table, adding further spice to a match between two sides from the same region.
Stuttgart have lost their last five games, which is why they can ill-afford another upset which would drag them even closer to the bottom three.
Yet Hoffenheim know that their hopes of avoiding relegation hinge on them winning these kinds of match, and the pressure is on.
"It is a very important game and we have got to throw everything into the mixer," said their coach Marco Kurz.
"Stuttgart are not in the stable form that they were in a few weeks ago, but we aren't either.
"I also don't see it as an advantage that Stuttgart were playing in the Europa League in midweek."
Stuttgart had hoped to gain some self-confidence from their clash with Genk on Thursday, but conceding an equaliser in stoppage time was the last thing they wanted with morale already low.
However, their director of sport Fredi Bobic, who fielded the reporters' questions while coach Bruno Labbadia was ill, said the team is not showing any signs of suffering from their current poor run of form.
"The lads have a fantastic mentality and we have all our faith in them," he said. "They are not giving up."