The Argentine clinched the La Liga title for the Spaniards at the weekend, scoring the only goal in a 1-0 win over Levante.
The semi-final first leg at the Nou Camp provides a tougher test for Ernesto Valverde’s side.
Messi will face the only English opponent he has yet to score against in Europe’s Premier club competition – albeit having faced the Reds just twice.
Here, Press Association Sport looks at Messi’s record against Premier League clubs.
It took the Argentina star until his ninth meeting with the Blues before he got his name on the scoresheet as the two teams shared some momentous Champions League battles.
He was shut out in the last 16 in 2005-06 – playing just 24 minutes in the second leg – the following season’s two group games and the semi-finals in 2009 and 2012.
He finally broke his duck last season after Andreas Christensen’s error in a 1-1 draw in the last 16 before scoring twice in a 3-0 win in the return leg.
Messi’s greatest individual night against English opposition came in April 2010 when he staved off a quarter-final upset with a stunning four-goal burst against Arsene Wenger’s Gunners.
His second-leg brace in the following season’s last-16 clash had a similar effect as Barca won 4-3 on aggregate, while he scored three of their goals in a 5-1 aggregate success at the same stage in 2016.
A hat-trick in October 2016’s 4-0 win in Group C, on Pep Guardiola’s return to the Nou Camp, boosted Messi’s record against City.
He also scored in the return fixture the following month, having previously found the net in both legs of Barca’s 4-1 aggregate win in the last 16 in the 2013-14 competition.
Prior to his two goals in this month’s quarter-final second leg, Messi had scored only twice in five appearances against the Red Devils.
Those goals, however, both came in finals – a header in 2009 and a superb 20-yard effort in 2011 – as he saved his best for the big occasion. The latter was his first goal on English soil.
This season’s competition was the first time Messi had come up against Spurs, who were drawn in Group B alongside Barca.
He marked the occasion with a brace in his side’s 4-2 win at Wembley, before playing just 28 minutes of the home fixture.
Not since the last 16 of the 2006-07 competition have the two clubs met, meaning Messi – who was just 19 at the time – has had to wait for his chance to show Liverpool what he can do.
He played the full duration of both games but was kept at bay as Liverpool won 2-1 at the Nou Camp and progressed on away goals after a 1-0 loss at home.
Join our new commenting forum
Join thought-provoking conversations, follow other Independent readers and see their replies