Work by Network Rail will see the mainline from Sussex to London close for nine days straight in February next year.
The line between Three Bridges and Brighton will close between Saturday February 16 to Sunday, February 24.
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The £67m upgrade – which has seen the line close on weekends throughout October and November – is set to improve track, signalling and drainage on the route which has become one of the least reliable in the south east of England, Network Rail said.
As well as the nine-day closure during the February half term, the line is also set to close on weekends in January and February.
A travel advice website to provide station-specific information to travellers has now been launched ahead of the nine-day closure, as well as a campaign which will see railway staff will be talk to passengers at two dozen stations over coming weeks.
Paul Harwood, Network Rail’s director of South East Route Investment, said: "We are reaching out to passengers with our train operator partners to make sure they are informed about the upcoming Brighton Main Line closures.
"By closing the line for one week in February we will be able carry out a huge amount of work simply not possible in more limited weekend closures, turning the Brighton Main Line from one of the least to most reliable routes on our network.
"I'd encourage passengers to take every opportunity to plan for their journey to make sure they can get to their destinations on time or make alternative arrangements."
Keith Jipps, Govia Thameslink Railway’s infrastructure director, said: "We've been pulling out all the stops to make sure passengers have been informed about the closures on the Brighton Main Line so far but now we really need to reach those passengers likely to travel during February half term.
“This work will be very disruptive and journeys will take longer. Passengers should log on to BrightonMainLine.co.uk for the most advanced information on how the closure will affect them and talk to our special closure awareness station staff at the sessions that have been arranged over the next couple of weeks."
Work to improve the line has already taken place at 25 separate sites and has included the renewal of 2.7 miles of conductor rail, 532 yards of track and 15 signals together with the replacement of thousands of tonnes of track ballast.
To find out more about the upcoming closures, visit: www.BrightonMainLine.co.uk