Porto may have it all to do in the second leg, but they do at least have a shot of reaching the semi-finals for the first time since 2003-04 when they went on to lift the trophy under Jose Mourinho.
Liverpool's emphatic win at this ground in February 2018 is the heaviest ever suffered by Porto on home soil in European competition. That was one of three away wins for the Reds in their four knockout-round matches since the start of last season, only emphasising the size of the task on the hosts' hands.
Porto also had to battle back from behind in the last round, though, overcoming Roma - the only side to beat Liverpool in a home knockout tie over the past couple of years - 3-1 here after extra time to cancel out their 2-1 loss from the first leg.
Since being thrashed by Liverpool last year, the Dragons have lost just two of their 10 European matches, both coming in the away legs of their knockout ties. At home, they have won four in a row and been victorious in six out of the last seven.
In fact, Porto are the only remaining side in the Champions League to have won 100% of their home games in the competition this season (4/4). They last won five or more straight home games in UEFA's elite club competition between October 1998 and December 1999 (a run of six).
This season's competition will also be remembered for incredible second-leg turnarounds, with Manchester United and Juventus recovering from two-goal deficits to beat Paris Saint-Germain and Atletico Madrid respectively in the last 16.
Behind Benfica on goal difference alone at the top of the Primeira Liga, Porto are still on course for a European and domestic treble. Conceicao's side can be proud of their efforts so far, but they will not want their European adventure to end just yet.
Recent form in Champions League: WWWLWL
Recent form (all competitions): WWDWLW
A cliche it may be, but every game for Liverpool between now and the end of the season really is like a final. Sunday's meeting with Chelsea certainly felt that way, explaining the scenes of joy at full time as the Reds claimed a cathartic 2-0 win.
It was their first win over Chelsea at Anfield in any competition since 2012, exorcising the demons from their infamous loss in the same fixture in 2014 when falling just short in the Premier League title race.
Liverpool were accused of throwing it away back then. They cannot be accused of the same five years on as they are on course to reach 97 points which, incredibly, may only be enough for second place.
That all comes down to Manchester City and how they hold their nerve, with big matches against Tottenham Hotspur and Manchester United to come for the defending champions. Liverpool, by comparison, face Cardiff City, Huddersfield Town, Newcastle United and Wolverhampton Wanderers in their remaining matches.
The pressure will be on Jurgen Klopp's men in each of those games, as will be the case at the Estadio do Dragao on Wednesday. Unlike their remaining four league matches, though, Liverpool can afford to draw - or indeed lose by a single goal - and still march on against Porto.
That is not to say Klopp can afford to make mass changes to his side, knowing just how easy it is for Liverpool's season to crumble with one negative result. They would not be the first side to challenge for multiple honours in the closing stages of the season, only to finish trophiless.
The two-goal margin of victory last week leaves the visitors in a very strong position, though, and history suggests that they should see the job through in Portugal.
Liverpool have progressed from all nine of their previous two-legged European ties under manager Klopp - four in the 2015-16 Europa League, one 2017-18 Champions League playoff and four Champions League knockout stage ties.
Maintain that run on Wednesday and it will be difficult for supporters not to get carried away.
Recent form in Champions League: LLWDWW
Recent form (all competitions): WWWWWW
Liverpool may be without skipper Jordan Henderson, a key player for them over the past fortnight in his more advanced position, as he sustained an ankle injury in the second half of the Chelsea match.
Klopp is confident that the damage is not serious and the England international will be given every chance to starting on Wednesday, though it is more likely that a back-up player will take his place.
Adam Lallana and Alex Oxlade-Chamberlain are unlikely to be part of Liverpool's travelling party, but Klopp can recall Andrew Robertson to his starting lineup after the full-back sat out the first leg through suspension.
Pepe's return allows Conceicao to revert to a four-man backline, meaning the versatile Eder Militao - off to Real Madrid in the summer - can shuffle across to right-back.
Vincent Aboubakar is close to a return after six months on the sidelines, but that is unlikely to come against Liverpool.
Porto possible starting lineup:
Casillas; Militao, Felipe, Pepe, Telles; Otavio, Pereira, Herrera, Corona; Soares, Marega
Liverpool possible starting lineup:
Alisson; Alexander-Arnold, Lovren, Van Dijk, Robertson; Wijnaldum, Fabinho, Keita; Salah, Firmino, Mane
Head To Head
Last week's victory for the Reds at Anfield leaves them with a record of four wins and three draws from their previous seven meetings with the Portuguese side.
Porto's record in two-legged ties with English clubs is won three and lost eight, losing each of the last five and going 15 years since last prevailing from a knockout tie against Premier League opposition.
We say: Porto 0-1 Liverpool (0-3)
Porto's positive home European record, coupled with the aforementioned round-of-16 comebacks, means that there is still plenty to play for on Wednesday night. Liverpool have won seven matches in a row, however, and that run is likely to extend in midweek to see them over the line.