Rail fares on the East Coast route are about three times more expensive than comparable routes in Belgium and France, a union has claimed.
GNER runs the East Coast route from London to Scotland
The RMT union also said the London-Scotland journey was more expensive per mile in Lincolnshire and Yorkshire than in other areas.
However, rail company GNER said the union's analysis was flawed as it used only the most expensive fares.
Off-peak day returns were cheaper than on French or Belgian railways, it said.
The RMT said GNER was expensive because it had to pay the Treasury £1 billion for its 10-year franchise.
"The RMT warned that the only way this money could be raised was by raising fares and cutting services," RMT general secretary Bob Crow said.
Comparing the cost of single-fare tickets, the union said a standard one-way journey from London to York (187 miles) costs £70, while in Belgium a similar journey would cost £22.68, and in France £22.25.
In a comparison of domestic prices, passengers travelling from London to York pay 38p a mile standard class and 63p a mile in first class on a return journey.
This compared with 34p a mile standard class and 52p a mile first class for the longer return journey between London and Newcastle.
Making a return journey between Edinburgh and London costs 25p per mile standard class and 36p per mile first class.
GNER disputed the union's analysis, saying it had used GNER's "most expensive, fully-flexible fares which are intended for the business peak."
Spokesman John Gelson said: "The comparisons between GNER fares and those charged by other organisations are selective and flawed as they do not tell the whole story."
He emphasised that large discounts apply for walk-up travel in the off-peak in the form of Saver tickets, and First or Standard off-peak advance purchase fares.
"French Railways in particular charge supplements for travel on some peak trains which can add 45% to the cost of a journey," Mr Gelson said.
"We are also cheaper than French or Belgian railways with most of our off-peak day-return fares."