But they have reassured passengers that all Ireland to Europe flights will operate as normal.
Ryanair released a statement on Tuesday afternoon confirming that 30 of 290 of Thursday's flights would be cancelled in an effort to alleviate stress on Ryanair staff.
"All customers who are travelling on flights to/from Ireland on Thursday 12 July who have not received any email or text notifications of flight cancellations should travel to their departure airport as normal", Ryanair said in a statement.
Scheduled flights between Ireland and the United Kingdom will face the brunt of the action, as Ryanair faces its second strike since recognising unions for the first time in December.
The airline said they have made alternative travel arrangements using both flights and ferries for nearly 5,000 passengers.
Why are pilots on strike?
The pilots' union Fórsa, of which the Irish Airline Pilots' Association (IALPA) is a branch, had earlier said it was not optimistic that a deal could be reached to avert the strike.
The claim was made after Ryanair made a dramatic u-turn on its industrial relations policy last December and agreed to recognise unions, when faced with strikes.
Ryanair's Irish pilots are set to strike today for the first time in the airline's 33-year history after talks broke down.
On Twitter, Ryanair said: "We respect but regret the decision of 25% of our Irish pilots to go on strike, but believe that they should take up our offer of working groups so we can resolve these issues".
"Ryanair pilots have already secured a 20% pay increase, earn up to €200,000 p.a., work 5 days-on, followed by 4 days-off (a double bank holiday weekend at the end of every week), enjoy rapid promotions and unmatched job security".
Last autumn, Ryanair was forced to cancel hundreds of flights after rostering failures left the airline with insufficient crew.
That is just ahead of planned strikes by cabin crew in Spain Italy, Portugal and Belgium on 25 July and 26 July.
The pilots union Fórsa said it was regrettable that Ryanair management had so far rejected the suggestion of third party assistance to break the deadlock.