The visitors, meanwhile, have lost five successive games to fall into the bottom three of the table.
Match preview
Having failed to win their final four matches prior to the enforced break in the domestic season due to the World Cup, Mainz have returned with real vigor in recent weeks.
Bo Svensson's side have taken 12 points from a possible 15 in their last five matches, with their 4-0 thrashing of Borussia Monchengladbach at MEWA Arena last Friday moving them up to eighth in the table.
Despite only having 36% possession across the course of the encounter, Daniel Farke's side were dismantled in a display of ruthless counter-attacking football, with Lee Jae-sung and Marcus Ingvartsen scoring either side of half-time, before Ludovic Ajorque and youngster Nelson Weiper wrapped up the three points for their side later on.
With their forthcoming opponents desperately out of form in recent weeks, Svensson will be determined for his players to seize the moment and continue their winning run on Saturday, especially with the European qualification places within sight for them.
Despite replacing Andre Breitenreiter with former Stuttgart boss Pellegrino Matarazzo in their managerial dugout in early February, Hoffenheim's fortunes are yet to turn around as their dismal form continued with a 1-0 defeat at home to Borussia Dortmund last weekend.
BVB dominated the proceedings from start to finish at Rhein-Neckar-Arena, amassing 25 shots in total, with Oliver Baumann forced into making 10 saves. Unfortunately for the experienced goalkeeper, he could not keep out Julian Brandt's effort two minutes before half-time, which ultimately proved to be the difference between the two sides on the day.
Die Kraichgauer have now collected just one point from their last 10 matches, winning only one of their last 16 games in the Bundesliga, so it is little surprise to see them sitting in the relegation play-off position after their most recent loss.
Matarazzo will be relieved that a strong start to the season under his predecessor has helped them avoid being cut adrift, but with VfL Bochum hosting Schalke 04 simultaneously to their trip to Mainz on Saturday, they are likely to require a positive result if they are to avoid sliding into the automatic relegation slots.
Mainz 05 Bundesliga form:
L
W
L
W
W
W
Mainz 05 form (all competitions):
W
L
L
W
W
W
Hoffenheim Bundesliga form:
D
L
L
L
L
L
Hoffenheim form (all competitions):
L
L
L
L
L
L
Team News
Mainz were dealt a major blow prior to their win against Gladbach with the news that their top goalscorer Karim Onisiwo would be out for at least five or six weeks with a knee injury, with Jonathan Burkardt still unavailable due to a similar issue.
Andreas Hanche-Olsen picked up a knock during his side's 4-0 victory and is likely to be sidelined for a few weeks, with Alexander Hack expected to replace him in defence on Saturday.
Anton Stach and Marlon Mustapha could be available for selection again after suffering with illness, while club captain Silvan Widmer will hope to recover his place in the starting XI after only appearing from the bench last time out.
Hoffenheim, meanwhile, will travel without Ozan Kabak after he sustained an ankle injury during his side's defeat to Dortmund last weekend. Ermin Bicakcic is expected to replace the Turkey international on the right side of the visitors' defence.
Robert Skov, Jacob Bruun Larsen, Justin Che and Grischa Promel all remain sidelined through existing injuries, but Dennis Geiger should return after missing out with a cold last time out.
The likes of Thomas Delaney, John Brooks and Munas Dabbur all provide potential solutions to Hoffenheim's distinct lack of form in recent times, having been unused substitutes against BVB.
Mainz 05 possible starting lineup:
Zentner; Fernandes, Bell, Hack; Da Costa, Barreiro, Kohr, Caci; Ingvartsen, Lee; Ajorque
Hoffenheim possible starting lineup:
Baumann; Bicakcic, Vogt, Brooks; Kaderabek, Rudy, Delaney, Angelino; Baumgartner; Dabbur, Kramaric
We say: Mainz 05 2-0 Hoffenheim
On current form there is only likely to be one winner at the MEWA Arena on Saturday, and we expect Mainz to live up to their recent performances by securing another victory.
Unless they can drastically turn things around, Hoffenheim look like a side destined to suffer their first ever relegation from the Bundesliga this season.