A project to improve drainage on the westbound side of the M58 near Ormskirk is due to take place this weekend.
The Highways Agency plans to resurface a section of the motorway to prevent surface water collecting on the carriageway following heavy rain.
The westbound side of the M58 will be closed overnight between junctions 3 and 1, from 10pm to 6am, on Friday, Saturday and Sunday night. Lane closures and a 50mph speed limit will also be in place during the day, with only one lane open to westbound traffic.
Drivers travelling towards Liverpool, including those heading to the Liverpool v Bolton FA Cup match at Anfield, are being advised to use alternative routes, such as the A580, and to allow extra time for their journeys.
Philip Deller, Project Manager at the Highways Agency, said:
We need to carry out this work to tackle issues with surface water on the westbound M58 but there will inevitably be some disruption while the resurfacing takes place.
We are publicising the closures as widely as possible and are advising supporters travelling to the FA Cup match at Anfield to use an alternative route, as only one lane will be open on the westbound M58 during the day.
The scheme is due to be completed by the early hours on Monday morning, so the motorway should be back to normal for commuters heading to and from work next week.
A signed diversion will be in place when the M58 is closed overnight, taking drivers along the A570 and the A59.
Members of the public should contact the Highways Agency Information Line on 0300 123 5000.
Journalists should contact the Highways Agency press office on 0844 693 1448 and use the menu to speak to the most appropriate press officer.