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Switzerland defeated World Cup winners France on penalties in the last 16 and captain Xhaka played a starring role on the night in a huge upset in Bucharest.
However, the Arsenal midfielder also picked up a yellow card - his second of the tournament so far - that means he is suspended for Friday night’s game in Saint Petersburg.
“It breaks my heart not to play - but I have full belief in us to get the job done,” Xhaka wrote on Instagram.
“What this squad have is special and we’re going to give our absolute everything to keep making history.”
Excitement is growing in Spain as they had feared a showdown with tournament favourites France, instead of Switzerland, in the quarter-finals.
Spain boss Luis Enrique, however, is not taking the Swiss lightly and urged his side against becoming complacent as they try to reach the last four.
“They are opponents that don’t gamble on throwing everything at you, that know exactly what they are doing,” he said.
“They attack and defend well, they play really well as a team and they make matches difficult for their opponent.”