Expectations will be sky high for Tite's men, with the South Americans just three wins away from a first World Cup title since 2002.
The prevailing theme of the Round of 16 of this World Cup - which is already being labelled as the best edition ever - has been the triumph of the underdog.
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But here they are after a huge upset win over Spain in a shootout to take on a squad in Croatia that faced their sternest test thus far when they defeated Denmark in the opening round of the knockout stage.
Among those still standing, Brazil and France represent the early favourites while Sweden and Russian Federation have advanced further than many would have expected, and all will be eyeing a run to the final after the unpredictable way this tournament has unfolded.
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The quarter-final clashes take place on Friday and Saturday. France produced 4 goals in their last outing, they have a fantastic midfield that can dictate pace, and enough attacking talent to score.
England may be more talented on paper but Sweden has a mojo rolling through this tournament that is hard to reconcile.
Sweden v England isn't the only game on Saturday.
They will face France or Uruguay should they beat the Belgians, before the final in Moscow against one of Russia, Croatia, Sweden or England.
The host country will hope that their fairy tale run in this tournament continues on Saturday, but Russian Federation once again has a mountain to climb if it wants to cause another upset.
Southgate said he was already looking forward to Saturday's quarter-final against Sweden in Samara, with a last-four clash against either Croatia or Russian Federation up for grabs.