"The first tests (in Peru) conclude that Paolo has pulled his cruciate ligament. This is very hard for us and of course for Paolo as well," coach Bruno Labbadia told reporters, after receiving a fax from Peru regarding the 25-year-old's injury.
"Paolo has scored most goals for us and has also had a leading role off the pitch," he said.
Guerrero, who leads the top-scorers' list with four goals in four Bundesliga matches this season, was due back in Hamburg on Friday and would undergo more tests there.
Guerrero, who had been taken off in Peru's 3-1 loss to Venezuela, is the second Hamburg player to be injured playing for his country after Namibian Collin Benjamin partially tore his cruciate ligaments in a friendly against Swaziland on Saturday.
Guerrero joined Hamburg in 2006 from Bayern Munich and has been a first-choice striker at the northern club since the beginning of last season.
"On a human level we are also affected because we know what they will have to go through now," said Labbadia.
"Now we have to all come together," Labbadia said of his team's Bundesliga clash against VfB Stuttgart on Saturday.
"We have to turn our stadium into a fortress," he said.
Hamburg are top of the Bundesliga on 10 points, ahead of Bayer Leverkusen on goal difference.
