"Saracens prop Mako Vunipola has been ruled out for the rest of the season and will miss the remainder of his club's Premiership campaign," the RFU said in a statement.
"Vunipola's hamstring injury requires surgery and will take a minimum of three months to recover."
England play Wales on Aug. 11 and 17, Ireland on Aug. 24 and then face Italy in a final warm-up game on Sept. 6.
They kick off their World Cup Pool C campaign against Tonga on Sept. 22.
(Reporting by Rohith Nair in Bengaluru; Editing by Simon Jennings)
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