Arsenal's Theo Walcott will miss the World Cup after being ruled out for at least six months with a knee injury.
The England forward, 24, was injured during the 2-0 FA Cup third-round victory over Tottenham on Saturday.
An Arsenal statement read: "Theo has sustained a ruptured anterior cruciate ligament of his left knee.
"He will have surgery in the near future and is expected to be out for at least six months, thus missing the rest of the season and the World Cup."
Walcott's Arsenal team-mate Aaron Ramsey wrote on Twitter: "Gutted for Theo, he'll come back stronger after this. Been fantastic for us so far this season. Have a speedy recovery mate."
The World Cup starts on 12 June, with England's first match against Italy two days later.
Walcott has been capped 36 times by the Three Lions, scoring five goals, with England winning 27 of those matches, drawing seven and losing just twice.
However, he sat out the final two World Cup qualifiers against Montenegro and Poland because of injury, with Tottenham's Andros Townsend excelling in his absence on the right wing.
The pair had been expected to be in direct competition for a starting place in Brazil under manager Roy Hodgson.
Walcott made his senior international debut as a substitute for Michael Owen in a friendly against Hungary on 30 May 2006, making him England's youngest ever player at 17 years and 75 days.
He is yet to play at a World Cup finals, despite being a surprise selection in Sven-Goran Eriksson's squad in 2006. Fabio Capello did not take Walcott to the 2010 tournament but the forward subsequently re-established himself under the Italian, earning selection for Euro 2012 and scoring in a 3-2 win over Sweden in the group stages.
Walcott's injury comes as a significant blow to club and country on the same day the Football Association said it would take no further action against him over his gesture to Tottenham fans as he was carried from the field during Saturday's game.
He did not appear to be in severe pain as he was carried off, signalling the scoreline to Spurs' supporters.
Arsenal boss Arsene Wenger said Walcott, who missed two months of the season with a stomach injury and has scored five Premier League goals since returning in November, was reacting to having coins thrown at him.
Wenger is expected to be without Denmark striker Nicklas Bendtner for all of January with an ankle injury, while France forward Olivier Giroud has missed Arsenal's past two games through a combination of illness and an ankle knock.
The Gunners lead the Premier League by a point from Manchester City and face Bayern Munich in the last 16 of the Champions League next month as they bid to end their nine-year trophy drought.
Walcott was signed from Southampton in 2006 for an initial £5m, rising to about £12.5m - a record fee for a teenager.
The Arsenal statement continued: "Everyone at Arsenal wishes Theo a speedy recovery and we look forward to seeing him back on a football pitch as soon as possible."
Former Arsenal defender and BBC pundit Martin Keown wrote on Twitter: "Shocking news for Theo Walcott, devastated for him.
"Hope he comes back stronger, he'll have a great medical team around him. Big loss."