Etsy, the online marketplace known for handmade goods, said it is cutting 140 staff in a bid to sharpen focus and improve results.
The announcement comes after an earlier round of layoffs in May and the resignation of the firm's chief executive.
Etsy, which became a public company in 2015, has struggled to turn a profit.
Competition has also mounted from other firms, including Amazon, which has launched its own handicraft market.
The two rounds of layoffs total about 230, or roughly 22% of the firm's workforce at the end of 2016.
Most of the cuts announced on Wednesday will come at the firm's Brooklyn headquarters, in positions such as marketing, product management and administration.
Founded in 2005, Etsy employed about 1,000 people globally at the end of 2016 and hosted about 25,000 sellers.
The company made $365m in revenue in 2016, but it has posted a loss every year since at least 2012, according to its annual report.
At least one of its shareholders has pressured the firm to consider selling itself. Two private equity firms - TPG Group and Dragoneer Investment Group - said last month they had taken a large stake in the company.
The firm said the layoffs would lead to as much as $8.8m in charges.