The hosts, meanwhile, must avoid defeat if they are to have a realistic chance of progressing from Group L.
Slovan Liberec were beaten by five goals to nil in the recent meeting between the two sides, with the Czech side having just 20% possession of the ball and only one shot on target against Hoffenheim.
In fairness, Pavel Hotfych's side are not exactly known for their proficient passing style, having gained their only win in this season's competition against Gent despite only having 29% possession during the victory.
Competing in the Europa League group stages for the first time since the 2016-17 campaign, simply being there is an achievement for a club of Slovan Liberec's size. However, Hotfych will certainly not allow his players to rest on their laurels, with progression to the knockout stages for the first time since 2013-14 still achievable.
He will certainly require a much improved defensive showing from his side if they are to have any chance of executing what is likely to be a defensive gameplan against their German opponents.
Hoffenheim may be winless in their last six Bundesliga matches, sliding down to 12th in the table in the process, but Sebastian Hoeness's side have made a faultless start to what is only the club's second ever Europa League campaign.
Three wins from three, scoring 11 goals along the way, means that a win in the Czech Republic on Thursday will see them through to the knockout stages of European competition for the first time in the club's history with two games to spare.
With Andrej Kramaric, who had not featured since late September after testing positive for coronavirus, finally returning to action in the 3-3 draw against Stuttgart at the weekend, morale and results may well be on an upward trajectory for Hoffenheim after a tricky period.
Given the disparity in quality between his side and Slovan Liberec in the recent meeting, Hoeness will be confident his team can get the job done on Thursday, potentially allowing him to rest players from what has been an injury-ravaged squad in the final two European matches.
Slovan Liberec Europa League form: WLL
Slovan Liberec form (all competitions): WWLLWL
Hoffenheim Europa League form: WWW
Hoffenheim form (all competitions): DWLWLD
Hotfych appears to be in the enviable position of having no injury or suspension concerns heading into the crucial encounter with Hoffenheim.
It is likely he will make a few changes from the 3-1 defeat to Jablonec at the weekend, though, with an extra defender likely to come into the side.
Hoeness, meanwhile, crucially has Kramaric back, though the Croatian forward may not be risked in this match. Sargis Adamyan, who scored a brace in the last meeting with Slovan Liberec, is unavailable due to coronavirus.
Slovan Liberec possible starting lineup:
Hasalik; Koscelnik, Mikula, Kacharaba, Pourzitidis, Kosek; Cancola, Nesicky, Hromada, Mara; Rondic
Hoffenheim possible starting lineup:
Baumann; Bebou, Posch, Nordtveit, Akpoguma, Sessegnon; Grillitsch, Samasseskou, Geiger; Baumgartner, Dabbur
We say: Slovan Liberec 1-3 Hoffenheim
We expect a much closer match than the previous meeting between the two sides, particularly if Kramaric is saved for the weekend as expected.
However, Hoffenheim should have enough quality either way to get the win they require to seal qualification to the knockout stages.
Top betting tip
body check tags ::