Fernando Santos's side are currently second in the group, but are just a point ahead of Serbia with two games left to play.
However, Portugal are hosting Lithuania next, who are bottom of the group and have just one point from their seven games so far, scoring only five times in that run.
With second-bottom Luxembourg to come in their final fixture, Portugal may feel confident of picking up maximum points and finishing second in Group B.
Here, Sports Mole looks at how the reigning European champions could line up for the visit of Lithuania.
With five members of the last Portugal squad missing, Santos is going to have to make some changes to the starting lineup that were beaten 2-1 away from home by group leaders Ukraine.
However, Wolverhampton Wanderers goalkeeper Rui Patricio is fit and will be expected to start in between the sticks against Lithuania.
Benfica defender Ruben Dias is likely to retain his place ahead of him at the heart of defence, as is Borussia Dortmund's Raphael Guerreiro at left-back. With Semedo out, Leicester City right-back Ricardo Pereira looks likely to replace him, while one veteran defender could replace another, with Jose Fonte coming in for Pepe alongside Dias.
Given the nature of the fixture, the more defensive-minded Danilo Pereira could drop out for Ruben Neves, who could partner club teammate Joao Moutinho in midfield. Ahead of them, Bernardo Silva should keep his place on the right, while Bruno Fernandes could play as a tucked-in option on the left flank in place of Guedes.
Cristiano Ronaldo will undoubtedly start in attack if he is fit, while Mario could be replaced with an extra striker as Portugal go for goals, with Andre Silva in line to partner to the Juventus star up front.