A decade playing for Manchester United's arch-rivals means Tuesday's Group A opponents are all too familiar to the Finn, who picked up his only red card at Old Trafford in 2003 and played his last full match in a Liverpool shirt there in 2009, helping his side to a famous 4-1 win.
"I knew only two days before kick off that I would play, that made it more special and I managed to play well, in the end it was my last 90 minutes in a Liverpool shirt," he told a news conference on Monday.
"Of course, I remember as well when I got sent off here after four minutes' play, I watched the rest of the game in the dressing room, we lost 4-0, so that wasn't a very good memory."
With a reputation as a cool and dependable defender who hardly ever got injured, Hyypia is a well known name in English soccer and his bright blond hair is as recognisable as it was before he left Anfield for Leverkusen four years ago.
He spent a couple of years playing for the German club before taking on a coaching role and the 39-year-old's rise to managing one of the country's top clubs has been eye-catching.
He was co-trainer with Sascha Lewandowski last season and the pair led the side to a third-place finish and when his coaching partner returned to his role in charge of the youth team in May, Hyypia took sole charge of the team.
Leverkusen have carried on this season from where they left off last term, taking 12 points from their opening five matches to sit third in the Bundesliga table.
Like his United counterpart David Moyes, Hyypia is managing in the group stages of Europe's elite club competition for the first time, but he reckons the pressure is all on the Scot.
"They are playing at home and they have big expectations in the Champions League this season, what happened last season (a last-16 exit in controversial circumstances at the hands of Real Madrid) - that can't be the same," he said.
"I think he (Moyes) is more under pressure. We can be quite relaxed and enjoy tomorrow. We need to give respect but not too much, we have to have courage to play football as we can, only then do we have the chance to get something from this game."
Hyypia, who won the Champions League with Liverpool in 2005, will be without midfielders Gonzalo Castro and Jens Hegeler after the pair picked up knocks over the weekend. Lars Bender faces a late fitness test.
One Leverkusen player United are very wary of is Stefan Kiessling, the Bundesliga's top scorer last season with 25 goals and who netted twice in their 3-1 win over VfL Wolfsburg on Saturday.
"He's a very important player for Leverkusen. He has to be given great respect," United manager David Moyes said.
"He's got a great record of goalscoring, both with his head and his feet, he's got a style for getting on the end of balls in the box so he's someone we'll have to watch very closely."
Kiessling's prolific form is in contrast to United's failure to score from open play in their last three matches and while Hyypia believes the English champions would soon remedy that, he hopes it will not be too soon.
"I don't think it's the first year that United are starting a bit slow," he said.
"David Moyes is an experienced manager, I think everyone should give him a little bit more time to get things running, hopefully that doesn't happen tomorrow that they get things running."