Avanti West Coast is strongly advising customers to check before they travel ahead of a strike by train managers on Sunday.
Members of the Rail, Maritime and Transport union (RMT) will walk out in a row over rosters.
A significantly reduced timetable will be in operation, with fewer services running during limited operating hours.
On Sunday, the inter-city operator will run one train per hour from London Euston to each of Manchester, Glasgow, and Liverpool, with services to Liverpool going via the West Midlands – including calls at Coventry, Birmingham International, Birmingham New Street and Wolverhampton – due to planned upgrade work by Network Rail between Rugby and Stafford.
Due to limited operating hours, the first train of the day will depart Euston just after 8am and the last train of the day from Euston will leave mid-afternoon at about 4.30pm.
The major upgrade work will also mean services to some destinations will have longer journey times as trains are diverted.
Due to the limited journey options, fans attending the Comic Con event in Liverpool are advised to find alternative transport.
North Wales, Shrewsbury, Chester, Blackpool and Edinburgh will have no Avanti West Coast services because the timetable is significantly reduced.
With fewer services running during shorter hours of operation, trains are expected to be busy and customers are strongly advised to check before they travel, including the details of their last train home.
The RMT said Avanti train managers are angry at having their work-life balance ruined, with significant cuts to rest days and short notice changes to shift patterns.
General secretary Mick Lynch said: “Avanti’s treatment of their staff is some of the worst we’ve seen in the industry and their overall mismanagement of the franchise is causing repeated cancellations for passengers.
“Avanti continue to operate with a siege mentality hoping that our members will simply give in.
“The truth is they need to negotiate rosters properly with our union and run the railway in a professional way.
“That seems a long way off and our industrial campaign will continue into next month.”