The 29-year-old, who has 51 caps for his country, will now play no part in Italy's Euro 2016 qualifier against Bulgaria on Saturday or face England in a friendly three days later.
“Unfortunately he sprained his right knee during training, no other player was involved,” said Italy's team doctor Enrico Castellacci on the FIGC website (www.figc.it).
“The player underwent an MRI scan at the Fanfani Institute in Florence, which confirmed subtotal damage of the anterior cruciate ligament. We have immediately informed Juventus medical staff and the player has already left the training camp.”
Marchisio's injury is a big blow for Juventus, who top Serie A by 14 points and are through to the quarter-finals of the Champions League where they will face Monaco.
He has been a mainstay of both the Italy and Juventus midfields for several years.
Italy, who are second in their Euro 2016 qualifying group behind Croatia on goal difference, will also be without Fiorentina defender Manuel Pasqual, who has also been ruled out.
"He suffered a contusion to his chest during his last league game, he still feels some pain and can’t give 100 percent”, said Castellacci.
(Reporting by Toby Davis in London,; editing by Pritha Sarkar)
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