If they beat the Lithuanians and, at the same time, in Belgrade, Serbia fail to beat Luxembourg, Portugal will seal second place in Group B and qualify for a competition in which they are the titleholders.
Despite a number of absentees, including Pepe, Nelson Semedo, William Carvalho, João Mário, Gonçalo Guedes and João Félix, Portugal are favourites to beat Lithuania, the group's last qualified team, with just one point, in what will be the first official duel between the two nations on Portuguese soil.
Cristiano Ronaldo, who has recently had some physical problems at Juventus, has a place in Fernando Santos' starting eleven.
In their first group match, Portugal beat Vilnius 5-1, with four goals from Ronaldo and one from William Carvalho.
Portugal-Lithuania is scheduled for 19:45 and will be refereed by Frenchman Ruddy Buquet. Three days later, Portugal play in Luxembourg for the last match in Group B.
The group is led by Ukraine (19 points from seven games), followed by Portugal (11 out of six), Serbia (10 out of six), Luxembourg (four out of six) and Lithuania (one out of seven).