The man behind their impressive turnaround over the past year and a half is 30-year-old manager Julian Nagelsmann, who is rapidly enhancing his reputation as one of Europe's best up-and-coming coaches.
But some Reds fans are not very confident about the clash.
The tie pitches Roberto Firmino against his former club as the Brazilian striker spent four seasons at Hoffenheim before joining Liverpool in 2015.
The 10 sides that win their play-off ties will enter the final 32 of the Champions League while the 10 losers will transfer to the Europa League group stage.More news: Southern Indiana Soldier Killed In Afghanistan Bombing
The first legs will be in Germany and Glasgow, on August 15th or 16th. Players and officials at Hoffenheim have been saying all summer that they are not scared of the extra strain of midweek games and high profile opponents.
Astana of Kazakhstan will have the opportunity to avenge last season's defeat to Celtic at the same stage.
Overall, Nagelsmann has made Hoffenheim a well organised and tactically astute team but the losses of Rudy and Niklas Sule to Bayern Munich might just weaken them.
"They won't be knocking back a few whiskeys just because they are playing us, but it's not as though we have no chance", said Nagelsmann.
Brendan Rodgers' side played Astana in the Champions League last season, drawing 1-1 away before winning the Parkhead return 2-1 thanks to a last-gasp Moussa Dembele penalty.