Ronaldo, Real Madrid's superstar forward, has been unable to inspire the sluggish Portuguese in their qualifying campaign and they are third in Group F with just four matches remaining.
Group leader Russia is one of only two teams with 100 per cent records in qualifying so far, so Portugal could be in even deeper trouble after the fulltime whistle in Lisbon.
Only the top team automatically qualifies for the finals in Brazil, with the eight best runners-up from the nine groups going into the playoffs. Fifth-ranked Portugal is a point adrift of the Russians having played two games more and also behind Israel on goal difference.
"It's essential we take all three points," Portugal coach Paulo Bento said. "We've run out of room for manoeuvr."
Portugal and England are the European powers most in danger heading into the second half of qualifying.
"(I) just can't picture a team like Portugal not making it to the World Cup," Portugal midfielder Joao Moutinho told FIFA.com.
With Spain, Germany, the Netherlands, France and England having the night off, Italy is the other power in action when it visits Czech Republic in Group B.
A victory would not only leave the Azzurri six points clear in their group, it would also take them to the Confederations Cup with some precious momentum. After playing in Prague on Friday, Italy is scheduled to fly to Brazil two days later for the June 15-30 tournament.
"Right now we've got to focus exclusively in the Czechs," Italy coach Cesare Prandelli said. "It's easy to look ahead to Brazil but this match is too important to be distracted."
Seeking its first appearance at a World Cup, Montenegro can pull five points clear of England at the top of Group H by beating Ukraine at home. Like Portugal, the English aren't even assured of second place, with Poland able to move to within a point of Roy Hodgson's side with a win at Moldova.
The battle for first place in Group A is between Belgium and Croatia, and they both lie on 16 points ahead of home games against Serbia and Scotland, respectively.
Austria and Sweden are vying for second spot in Group C behind runaway leader Germany ahead of their meeting in Vienna while the top three in Group E — Switzerland, Iceland and Albania — are all in action with just two points separating them.
Group leader Switzerland is at home to Cyprus on Saturday while Iceland, two points further back, hosts Slovenia on Friday and Albania is at home to Norway.
Bosnia-Herzegovina would stay in control of Group G by beating Latvia away, with second-place Greece three points adrift ahead of its game at Lithuania.