Drainage work in Nathan Road has caused shops and restaurants heavy losses over the past five months, forcing some to shut, shopkeepers said.
The northbound carriageway between Boundary Street and Nullah Road has been closed since October for anti-flooding work and will reopen on Sunday.
But work lasting 7.5 months will begin in the opposite lane on the same day.
Shopkeepers said the work caused loud noise and dust pollution, and the relocation of bus stops had diverted customers.
'We have lost 70 per cent of our business since last October,' said Mrs Lee, whose leatherwear store will close this month.
She owes three months' rent and is selling her imported leather coats - discounted by 70 per cent - at a loss.
'They began the works in October just as it was getting cold and are finishing just as it's warming up,' Mrs Lee said.
Electrical store owner Wong Siu-yuen said business in the past five months had been at its 'worst in 20 years'.
'The bus stops are gone and people cannot see our shop,' he said. 'We've really struggled to make it through.' Mongkok shopkeepers demanded compensation last October but received nothing. They complained the Government did not provide enough consultation and proprietors had no chance to renegotiate rent with landlords.
Shopkeepers on the southbound lane are less critical about the impending works.
'I prefer it that the works are done while the economy is bad and we have no customers,' said Alex Yeung Hung-po, owner of International Fashion.
The Drainage Services Department said that even with the completion of work, there was no guarantee flooding would be eradicated.