The Portugal winger believes the Three Lions will falter in their first two games in Ukraine and Poland without the suspended striker but backs his own team to succeed
Roy Hodgson will instead have Andy Carroll, Jermain Defoe and Danny Welbeck to choose from up front for their first two group games.
Nani, 25, hopes the Three Lions reach the knock-out stage but believes his Manchester United team-mate’s absence will harm the nation’s chances of success.
“Rooney is a key man and two matches without my United companion could be too much for England,” he told The Sun.
“Roo is angry about his absence because he knows he's the man to score goals and he won't be there working for the team.
“I sincerely want England to reach the quarter-finals but it's not going to be easy.”
England have suffered with several injuries since Hodgson named his 23-man squad, with Frank Lampard, Gary Cahill and Gareth Barry all having to pull out in the last two weeks.
Nani said: “For an England team without Rooney, Rio Ferdinand, Frank Lampard and Gareth Barry is vulnerable because they are suffering in all departments of the team.
“These players are so important for the team and their replacements are not at the same level.
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“These absences place many doubts about the English for the Euros. England need to make their biggest effort because injuries are destroying the team.”
The Portuguese believes the victor of England's first group clash against France will likely go on to top the group, and also hailed his own side's chances of success, despite being drawn alongside Germany and Netherlands.
“England's opening game against France is very dangerous,” the Old Trafford winger explained. “The two teams both need a victory because the result will put a very decisive stamp on the group.
“The losers will receive much criticism and that will generate a lot of pressure for the following game.
“People consider Spain, Germany and Holland as the big candidates for the European Championships but Portugal can spring a surprise.
“If we can gain confidence from one match to the next, we can go a long way.”