The technology firm said between 25,000-30,000 roles would go at HP Enterprise, a business it is creating to bundle together its data analysis and software divisions - separating them from the personal computer and printer operation.
The move is due to be completed by the end of October and HP said the job losses, which follow 55,000 cut over the past three years, were part of efforts to reduce costs by $2bn per year.
It was unclear at this stage whether any of its staff, numbering around 15,000 in the UK and Ireland, would be affected.
HP announced the spin-off a year ago amid the market shift from PCs to mobile devices that has reduced demand for many of the company's key products.
Chief executive Meg Whitman, who will lead HP Enterprise, told investors she expected it to rake in more than $50bn in annual revenue.
""HP Enterprise will be smaller and more focused than HP is today, and we will have a broad and deep portfolio of businesses that will help enterprises transition to the new style of business.
"As a separate company, we are better positioned than ever to meet the evolving needs of our customers around the world."
Its share price has lost 33% of its value in the year to date on the New York Stock Exchange.