Following on from Madrid's 4-0 thumping of Tottenham, Barca appear to have done all the hard work in their home quarter-final tie and have one foot in the next round ahead of the return leg in Ukraine.
Pique, who was also on the scoresheet in midweek, insists Pep Guardiola's side will not be getting too far ahead of themselves, but admits the prospect of a clash with their arch-rivals would be sensational.
"We have to remain focused on us and try to keep doing better. If we can get to the semi-finals and play against them [Real], it will be a great game," Pique told Sky Sports. "I think everyone wants this because there is a lot of rivalry between the two teams.
"Barcelona and Real Madrid are two of the most important teams in Europe and it will be a great game if finally we qualify Madrid and Barcelona."
But Pique knows the job against Shakhtar is only half done and did not expect things to go so well at the Nou Camp.
"They are a great team and it is always difficult to play against them," he said. "I think that we played really well and 5-1 is a great score to take to the Ukraine.
"They have really good players, really good strikers that are really quick and are Brazilian with a lot of skill and quality. We have had to work really hard and I think we did a good job."