Mr O'Brien said he made the decision "to avoid any further impact to the delivery of health and social care services"
Tony O'Brien is to step down as Director General of the HSE tomorrow.
The HSE confirmed the news in a statement this evening, as Mr O'Brien faced increasing pressure in the wake of the Cervical Check scandal.
Mr O'Brien - who had previously insisted he wouldn't resign - will step down from close of business tomorrow.
The executive said: "Mr O’Brien said that he has made his decision in order to avoid any further impact to the delivery of health and social care services, and in particular the cancer screening services that have become the focus of intense political debate in recent days.
"He said, notwithstanding the clear communication failures surrounding the Cervical Check Audits, he is confident that the Scally Review will demonstrate the quality and value of the Cervical Check Programme once it is complete."
Press Statement - Director General of HSE Tony O’Brien - https://t.co/Zaq0xoOYsw— HSE Ireland (@HSELive) May 10, 2018
In a statement, Health Minister Simon Harris said he had met with Mr O'Brien this evening.
Minister Harris said: “I would like to express my thanks to Tony O’Brien for his many years of dedicated public service.
"I know that he is standing down from his role today because he believes it is in the best interest of rebuilding public confidence in the wake of the issues which have arisen in CervicalCheck."
Mr O'Brien's decision followed intensifying pressure from opposition politicians for the HSE chief to resign in the wake of the cervical screening scandal.
Fianna Fáil had earlier indicated it would back a Sinn Féin motion of no confidence in Mr O'Brien next week, while independent Minister Katherine Zappone had also publicly expressed her view that the HSE boss should go.
It also comes following the release of a memo to the HSE in 2016 showing that Cervical Check had prepared a response for media stories about screenings not diagnosing cancer.
The Cabinet is meeting in Dublin tomorrow to discuss the cervical screening controversy - including "further measures which can be put in place".