In Ronaldo's absence, his Manchester United teammates, Bruno Fernandes and Diogo Dalot inspired Portugal to return to winning ways.
Portugal vs Nigeria - First half
A dominant performance in the first half saw Portugal wrap up preparation for the FIFA World Cup in some style.
Nigeria's Super Eagles were no match and hardly put up a fight as Manchester United duo Bruno Fernandes and Diogo Dalot inspired the former European Champions to a convincing win.
Fernandes and Dalot combined superbly to put Portugal in front after just nine minutes at the Jose Alvalade.
Fernandes made it 2-0 from the spot after the referee awarded what looked like a soft penalty after the half-hour mark.
Just before the break, it could have been 3-0 for the home side but the Super Eagles had their blushes by Joao Felix, who failed to convert from close range.
Portugal vs Nigeria - Second half
The second half was an evenly contested encounter between the two nations as Nigeria looked better than in the opening half.
Portugal took their legs off the pedals but the Super Eagles still struggled to find a way around their defence.
Despite an improved performance by the Nigerian side, the home side looked the most likely to add to the scoreline.
However, Nigeria got a lifeline when the referee awarded a penalty nine minutes from time but substitute Emmanuel Dennis stepped onto the plate and watched his kick saved by Rui Patricio.
Moments after the miss, Portugal extended their lead to 4-0 after two goals in the space of two minutes.
Goncalo Ramos made it 3-0 for his debut goal for Portugal before Joao Mario wrapped up proceedings with a fourth two minutes later.