Books on the Park, on Ecclesall Road, is nearing the end of its lease and will shut by the middle of May.
Owner David Granville first warned his business faced closure in January, blaming high rents, the effect of internet sales and the dominance of charity shops for the decision.
"It's not the news that our customers, friends and supporters of independent second-hand bookshops will want to hear but, having failed to find suitable alternative premises, Books on the Park will be closing down sometime between the end of April and the middle of May," he said in an update to supporters.
None of the new places he had considered met the required 'size, location or cost'. David will continue to trade online as Starryplough Books, but even that venture is at risk, he claimed.
"The way things are going with the main online platform that we use - the behemoth that is Amazon - this might not be for much longer either. It appears a series of changes made over the last 12 months seem designed to force smaller, independent sellers to seriously consider it’s no longer worth the candle."
An end of lease sale has been extended, but some stock will be moved into storage 'just in case something crops up later in the year'. "If it doesn’t, this will have to be disposed of as well."
The shop, which deals primarily in second-hand editions, has traded at various sites across from Endcliffe Park over the past 15 years. It presently occupies a corner spot opposite the junction with Rustlings Road.
Recent figures from the Booksellers Association offered hope the sector had turned a corner, as in 2017 the number of shops not part of a big national chain increased, rather than declined, in the UK and Ireland for the first time since 1995. But the report only covered independent outlets selling new books.
"While high rents are probably the most important, no one factor alone is responsible for the problems that independents face," said David in January. "However, together they can, as we have found, add up to something of a perfect storm."
Last July another well-known second-hand bookshop, Rare & Racy, closed on Devonshire Street in the city centre after 50 years after plans to demolish it were approved. And elsewhere on Ecclesall Road, Napoleons has shut its casino amid claims from boss Dave Allen that the street 'is not what it used to be'.