The TU Dublin Aungier Street Campus is being brought to the market for sale through estate agents CBRE with a guide price of €110m.
D2HQ, situated very close to St Stephen's Green, is the most prominent city centre development site to be offered to the market in Dublin in the last 12 months.
The site has development potential - subject to planning permission - to deliver a brand new urban quarter in the heart of Dublin 2.
It extends to 2.5 acres and is zoned Z5 City Centre under the Dublin City Development Plan 2016-2022, which offers the buyer the potential to provide for a mix of uses including offices, retail, residential, hotel and student accommodation.
The sale comes almost a year after the slightly larger TU Dublin campus on Kevin Street was sold for €140m.
The sales are part of the university's shift northwards to the centralised campus of Grangegorman in Dublin 7.
Technological University Dublin will welcome 10,000 students and staff to its new flagship campus in Grangegorman in September.
When complete, it will have more than 20,000 students and 2,500 staff on the 73-acre site.