An application to replace the 160-year-old Greyhound Hotel with 43 apartments and five shops has been filed with Port Phillip Council.

A decision on the application will be made by February, but the hotel can be knocked down at anytime. It is not subject to any heritage protections.

A private building surveyor has already issued a building permit for the demolition of the pub, which is located opposite St Kilda Town Hall.

A campaign to save the venue, also known as the GH Hotel, is gaining steam, with more than 1500 people signing an online petition urging the developers not to "pull down another great icon of Melbourne for more bloody apartments".

St Kilda resident Caroline Thurling said there was growing concern St Kilda was losing its character with the ongoing destruction of old buildings in the beachside suburb.

"I have had visitors and friends come to the area commenting on how much St Kilda has changed and how bland it's starting to look," Ms Thurling said.

"You just need to drive around the area and see where an older building would have been, or you'll see tall apartment building going up.

Ms Thurling described the plans for the Greyhound Hotel site as "generic" and "not in keeping with the neighbourhood character, which is that old Melbourne feel".

"Ideally you want to keep St Kilda's character but if you want to do a completely modern development, well let's have some sophistication in design," she said.

Port Phillip mayor Bernadene Voss said while "there was affection within our community for the Greyhound", a preliminary heritage assessment found the pub did not have architectural significance.

"It also questioned the building's capacity to qualify for heritage significance on social, cultural or spiritual grounds," she said.

The Greyhound Hotel is one of a long line of drinking and entertainment venues to be threatened or closed around St Kilda.

Those already relegated to the history books include The Palace, a popular venue for all night raves in the 1990s, and The Venue, which hosted Cold Chisel and INXS when it first opened in the early 1980s.

Burger bar Greasy Joe's once turned into a full-on late night party after the kitchen closed, where one night a policewoman was photographed dancing on the bar after hours.

Professional drag performer Amanda Monroe used to perform at the Greyhound Hotel and said in its heyday that it was "the drag capital of Melbourne".

"To quite a few generations of people it was the place they went to discover themselves, to know they weren't the only person in the world," she said.

"They went there and found lifetime friendships."

However Ms Monroe said the club had been struggling in recent years.

"They have tried a whole range of activities to try to inspire interest, but the newer generation is looking for something that isn't a giant venue with big productions."

The pub is owned by Chris and Will Van Der Linden, but is managed by Karina Harcourt's CWK Hotels.

Ms Harcourt said the hotel had not been making money for quite some time, and she had been told the permit application was "more of a back-up option" if the business did not turn around.

She said the club was quite expensive to run due to the performances it hosted.

Earlier this year Port Phillip Council promised to investigate whether there were other old, unprotected buildings that could be considered socially significant after a demolition permit was granted for another old pub, The London.

That work is ongoing, said Cr Voss.

The last substantial heritage review in Port Phillip occurred 20 years ago, but Cr Voss said it "has been updated on an ongoing basis ever since".