Guerreiro limped off the pitch after 66 minutes of his side's 1-0 victory over hosts Russia in Moscow on Wednesday.
And Portugal boss Fernando Santos is worried the Borussia Dortmund star, who had earlier set up Cristiano Ronaldo's headed winner, has suffered a serious injury.
"Raphael went to hospital," he said. "We think he might have fractured his leg, unfortunately.
"That was a bad moment for Portugal. He is a fantastic boy and he played very well.
"He is a top quality player and this might have an impact on the beginning of his new season as well.
"We are sad about that, but let's see what the exam results tell us. I hope they are not as serious as we believe they are at the moment, I hope not."
Guerreiro, 23, was part of Portugal's victorious Euro 2016 team and joined Dortmund from Lorient in a reported €12million move ahead of the 2016-17 season.