Eric Pickles confirmed that he supports the plans for Old Oak Common.
The development in north-west London will create up to 24,000 homes and more than 55,000 jobs, according to the mayor of London's office.
Labour Hammersmith MP Andy Slaughter said he feared the scheme "may not be in the interests of local people".
"I am concerned the project could end up working primarily for big developers to exploit the land for their own interests, not the interests of local people or local councils," the MP said.
"I am all in favour of regeneration but big developers like this need to ensure that they build housing for Londoners; it cannot be all 'ghost' housing for overseas investors."
A vast High Speed 2 (HS2) and Crossrail station is due to be constructed at Old Oak Common by 2026.
The new station would be the size of Waterloo, handling 250,000 passengers a day and acting as a super hub between London and the rest of the UK.
In 2013, Queens Park Rangers Football Club confirmed it was in talks over building a new 40,000-seat stadium as part of a redevelopment scheme at Old Oak Common.
On Tuesday, London's deputy mayor for policy and planning Sir Edward Lister told the Financial Times he was supportive of the idea of a stadium in the area and was in discussion with QPR and current landowner Cargiant about possible locations for a football arena on the site.
"We would like to see one there but it's a matter of trying to find a suitable place," he told the newspaper.
QPR chairman Tony Fernandes responded on the club's website, saying: "Old Oak Common has been identified as an area where the club's new home can be housed."
The development will deliver a Â£15bn boost to London's economy over 30 years, London mayor Boris Johnson has claimed.
He said: "The vast new station at Old Oak Common presents us with an almost unprecedented opportunity to transform an area the size of a small London borough into a thriving new part of the capital, with unrivalled transport links to central London, the rest of the country and beyond."
Mr Pickles said: "House-building is a key part of the government's long-term economic plan. So it is absolutely right that delivering new homes is at the heart of this exciting regeneration scheme."
One of the largest regeneration schemes in London for decades has been approved by the secretary of state for communities and local government.