Wilkies, which sells a range of fashion and footwear for men and women, is calling time on the business after 28 years of trading in Bank Street.
The news follows the closure of the shoe shop Clarks, where nine jobs were lost in June.
Other recent closures have included the jewellers H Samuel and the clothes store Bonmarche.
Amid the retail gloom, national retail chains Argos and Poundland have both stated their continued commitment to the town.
A statement on Wilkies Facebook page has confirmed the bad news, saying: “It is with much sadness that we announce the closure of Wilkies in Galashiels after 28 years trading in the town. In order to clear stock before the doors close in January prices will be slashed with a closing down sale starting on Monday, November 23.”
Galashiels and district councillor Euan Jardine said: “It’s really disappointing to see another store in the town close its doors. My thoughts are with those that have been effected by the closure. Unfortunately, high streets across the country which were already in a fragile position at the start of the year are facing a real difficulty to recover due to the ongoing pandemic.
“The executive committee passed a paper at Scottish Borders Council last week which will waive car parking fees in town centres from early December until the beginning of January. I really hope this will encourage people to shop local this festive period and give the high street the boost it needs.”