On Thursday, German pilots joined striking pilots in the Netherlands and Belgium adding another 100 to the 150 cancellations already in the pipeline.
Cabin crews in Belgium, Germany, Italy, the Netherlands, Portugal and Spain are also stopping work in a row over contracts and conditions.
So far, relatively few flights to and from the UK seem to have been affected.
The travel editor of the Independent, Simon Calder, said Stansted Airport, which is Ryanair's biggest European hub, had seen about 20 flights cancelled. These were mostly to and from Germany.
He said eight Manchester services - to and from Barcelona, Berlin, Faro and Malaga - have been grounded, as well as flights from Birmingham to Lanzarote and East Midlands to Malaga.
Unions want staff to be given contracts in the countries where they live, rather than under Irish law.
Chief executive Michael O'Leary said the company had written to unions offering to move all staff to local contracts, which made the strike action "unnecessary".
However, the Dutch pilots union said it had only verbally offered its members local contracts and had refused to put the offer in writing.
Joost Van Doesburg, of the VNV union, said his members also wanted pensions in line with Dutch standards, and firmer guarantees on sick pay.
Tom Burridge, BBC transport correspondent
Meet with Michael O'Leary and beyond the bullish facade, this multi-faceted dispute is more complex and potentially damaging than he is willing to let on.
The roots of today's row stretch back to autumn last year when Ryanair 400,000 Ryanair passengers had their flights cancelled.
The airline did not have enough pilots to honour its schedule. It was in Mr O'Leary's words "a mess of our own making".
The subsequent decision to start recognising pilot and cabin crew unions around Europe was a multinational can-of-worms.
Some deals with some unions in some countries have been done.
But overall there is plenty to resolve and incendiary language, on both sides, is the flavour of the day.
Ryanair this week signed deals with cabin crew unions in Italy to provide employment contracts under Italian law and agreed to arbitration with the union representing its German pilots.
The European Commission said Ryanair employees should have contracts in the countries where they live rather than in Ireland, where its planes are registered.
EU social affairs commissioner Marianne Thyssen told Mr O'Leary at a meeting in Brussels on Wednesday that EU rules on employment of air crews were based on where workers left in the morning and returned in the evening - and not where aircraft were registered.
"Respecting EU law is not something over which workers should have to negotiate, nor is it something which can be done differently from country to country," Ms Thyssen said.
"The internal market is not a jungle - it has clear rules on fair labour mobility and worker protection. This is not an academic debate, but about concrete social rights of workers."
Ryanair has traditionally employed a large proportion of its staff under Irish law, which unions say inconveniences workers and affects their ability to access social security benefits
Ryanair said the vast majority of its 2,400 flights on Friday would be unaffected, with only 35,000 of 450,000 passengers experiencing disruption.
Passengers whose flight have been cancelled were contacted by email and text message on Tuesday to advise them of their options.
"We sincerely apologise to those customers affected by these unnecessary strikes on Friday which we have done our utmost to avoid," Ryanair said.
It has rejected calls by the UK's Civil Aviation Authority to compensate passengers whose flights have been cancelled, claiming they were caused by "competitor airline crew, unions and lobby groups" and were therefore "extraordinary circumstances".
However, Coby Benson, a lawyer specialising in flight delay compensation at Bott and Co, said Ryanair's arguments did not comply with the precedent set in April by a case in Germany.
Last month, Ryanair pilots across Europe staged a coordinated 24-hour strike to push their demands for better pay and conditions, plunging tens of thousands of passengers into transport chaos at the height of the summer holiday season.
In July, strikes by cockpit and cabin crew disrupted 600 flights in Belgium, Ireland, Italy, Portugal and Spain, affecting 100,000 travellers.
Another indication of the company's rethink on contracts came on Thursday when it announced two new bases in France. They will be the first in the country since it closed Marseille in early 2011 after being sued for employing French workers on Irish contracts.
It will also open another base at Bordeaux for summer 2019 and had another four under consideration.
Two aircraft will be based at both Marseille and Bordeaux and will offer a total of 64 routes and handle 3.5 million passengers a year.
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