The former Manchester United man is outspoken in his views of Los Blancos and the situation regarding Catalan independence, a topic that has caused discontent among some Spaniards.
The 28-year-old has faced abuse from his own fans while on international duty and was jeered by a number of supporters during Spain's Euro 2016 qualifying win against Slovakia in Oviedo.
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He also received similar treatment back in June when the 2010 World Cup winners faced Costa Rica in Leon.
Spain's upcoming friendly against England has also been moved away from Real Madrid's Bernabeu stadium to the coastal town of Alicante amid fears the Barcelona man will once again face abuse from supporters.
Barca boss Luis Enrique has leapt to the defence of his central defender saying it is 'pathetic' that a player gets booed while on international duty.
As per Marca, he said: "Do I always want Real Madrid to lose too? Piqué is an honest guy. We need this rivalry between our clubs.
"Guti said the same back in the day. I think it's pathetic to boo a footballer playing for our national team. It's ridiculous that these things happen in this country".
Pique has insisted he will never turn his back on his country and will continue to play in spite of the jeers.
The central defender is back on club duty and gearing up for a huge game against Atletico Madrid. If Barcelona can take all three points they will hold an early advantage over both Madrid clubs.