The demonstration came hours after a similar protest forced the closure of Manchester Piccadilly railway station.
Among those present at the station was Chris Woodhouse, who said families were in tears on the platforms as trains bound for airports were among those cancelled because of the demonstration.
Around 100 protesters holding the so-called flags of the terrorist group invaded one of the two biggest stations in Manchester before moving onto tracks.
The demonstration follows several months of conflict between Kurdish groups and Turkish forces in Afrin, northern Syria.
Witnesses say some passengers were in tears and faced long delays getting out of the station, which is now closed.More news: Mindy Kaling got 'the most useful' parenting advice from Reese Witherspoon
The National Rail said there was only one exit now functioning at the station as police were addressing the chaos caused by the protesters.
'Passengers are advised that all lines are suspended in and out of Manchester Piccadilly.
Police were called shortly after 1pm and all trains through the station stopped, with knock-on effects nationwide.
The National Rail Twitter account wrote: 'The station has been closed due to a protest gathering.
Disruption is expected to last until around 4.30pm, National Rail has said. More info when we have it'.