Both nations are under new management, looking to improve on respective disappointments in recent months.
Match preview
For the first time in nine years, Portugal will take to the field not managed by Fernando Santos, after their Euro 2016-winning manager left his role following an underwhelming performance in the World Cup.
A quarter-final defeat to Morocco was a markup on last-16 exits at Russia 2018 and Euro 2020, but ultimately was seen as yet another failure with such a talented group of players.
Roberto Martinez has come in to replace Santos after also leaving his role as Belgium boss in the aftermath of a group stage exit in Qatar, in an appointment that has raised some eyebrows.
Martinez largely struggled to get the best out of a Belgium squad stacked full of world-class players, and there is a fear that with a similar abundance of quality at his disposal in the Portugal squad, they may underperform again.
After losing four of their last nine games under Santos, and struggling through World Cup qualifying, there will need to be an evident improvement quickly under Martinez, as the Spaniard will not have any goodwill stored up to fall back on like Santos did for winning the Euros in 2016.
This should be a straightforward encounter for them to navigate first up though, facing the bottom seeds and arguably the most out-of-form team in European international football.
Liechtenstein were the worst performing side in the last edition of the UEFA Nations League, finishing bottom with zero points in League D.
Defeats home and away to Andorra, Latvia and Moldova also saw them score just one goal, as they had a worse record than San Marino in League D's other group.
Recent results also include a defeat to Gibraltar, a 6-0 thrashing at the hands of Cape Verde, and a 9-0 loss to Germany, the last time they faced a side in the world's top 50.
Liechtenstein are now ranked 198th in the world, their lowest ever position in the rankings, having gone 13 games without a win, losing 11.
Martin Stocklasa left to join FC Vaduz at the start of the month, so Rene Pauritsch has come in as caretaker manager for this international window following five years at the helm between 2013 and 2018.
Pauritsch has a huge job on his hands though to improve upon records such as scoring just four goals in their last 20 European qualifiers.
Their record against Portugal is an even more sobering sight, as they have conceded 35 goals in seven meetings, including two 8-0 defeats away from home.
Portugal form (all competitions):
W
W
W
L
W
L
Liechtenstein form (all competitions):
L
L
L
L
L
L
Team News
Cristiano Ronaldo has been named in the Portugal squad despite his move to Al Nassr at the start of the year.
With a record 118 international goals already to his name, Ronaldo will hope to be on the pitch here to add to that tally.
Pepe was initially named in the squad, but the Porto defender has since been ruled out with the injury which saw him miss his club side's Champions League second leg with Inter Milan last week.
Overall, there are very few changes to the squad which was taken to the World Cup, despite the change in manager.
Six of the Liechtenstein squad play at FC Vaduz, who enjoyed Europa Conference League football earlier in the season.
With the club near the bottom of the Swiss second tier though, that is a low number compared to their recent dominance of the squad.
Noah Frick, son of all-time top scorer Mario Frick, is in the squad, but his brother and teammate Yanik Frick has been left out.
Captain Nicolas Hasler is the all-time active appearance holder and goalscorer, but his offensive capabilities are unlikely to be called upon much in this one.
Portugal possible starting lineup:
Diogo Costa; Cancelo, Danilo, Antonio Silva, Guerreiro; Ruben Neves, Bernardo Silva, Fernandes; Joao Felix, Ronaldo, Rafael Leao
Liechtenstein possible starting lineup:
Buchel; Yildiz, S Wolfinger, M Wolfinger, Hofer, Traber; Hasler, Sele, Luchinger, Weiser; Frick
We say: Portugal 7-0 Liechtenstein
In a clash between top and bottom seeds in Group J, this appears to be a complete mismatch on paper.