A series of voters and business leaders told LBC Radio that Mr Johnson would not win in the constituency unless he reverses his call for Heathrow to be shut down.
Mr Johnson described Heathrow as “a dead duck” and said he will “fight to my dying breath” to halt a third runway.
Some Conservatives feel that Mr Johnson’s return to Parliament will destabilise David Cameron because it will lead to intense speculation about Mr Johnson’s leadership ambitions.
Mr Johnson yesterday appeared to challenge Mr Cameron’s position on the European Union by insisting that reforming Britain’s relationship with Brussels would be “easy”.
The Mayor this week said that Britain has “nothing to fear” by voting to leave the EU in an in-out referendum if Mr Cameron is unable to change the UK’s relationship with Brussels.
In an interview with the Evening Standard, he rejected claims that the reforms he is demanding will be impossible to achieve in time for the referendum Mr Cameron has promised to hold in 2017.
Mr Johnson said: “I’m not so pessimistic. I think you could easily.”
In the interview, Mr Johnson disclosed that he has been included on the official Conservative candidates list, allowing him to stand in Uxbridge.
One London Tory MP said Mr Johnson would have to “temper” his views on closing Heathrow and building a new airport hub to the east of London.
Another Conservative said: “This could be a real problem. The seat has a majority of 11,000 but thousands of people who work in Heathrow live in the constituency and many thousands more are reliant on the airport for their incomes. He may have chosen the wrong place to stand.”
Chris Summers, the Labour candidate standing in the constituency, said: “So many people in Uxbridge and South Ruislip either work at Heathrow or have businesses which rely very much on it.
“They will be distraught that somebody who is [standing is] so hostile to Heathrow and actually wants it to close down.”
Bill Gritts, who runs Wings coach service, said: “In the surrounding areas it would have a major, major effect.”
He added: “If this is his manifesto for him to become the MP for Uxbridge, then I don’t think he is going to end up as an MP for Uxbridge.”
Other seats Mr Johnson is thought to be considering include Hertsmere and Hornchurch and Upminster.
To be party leader Mr Johnson has to win over backbench MPs and he has been courting the 2010 intake, which accounts for more than half of the Conservative Parliamentary party.
However, there is less support among him among older MPs from the 2005 intake and earlier who remember his unsuccessful stint as an Opposition education spokesman.
One senior member of the backbench 1922 committee is known to be particularly disparaging about Mr Johnson’s chances of advancement once he is an MP.