The A38 is closed in both directions between Branston and Burton due to flooding.
Police say a severe flood warning is in place in the Burton area meaning there is a threat to life.
A Facebook post from East Staffordshire Police said: "A decision has been made to close the #A38 Southbound at #Branston and Northbound at #Barton due to flooding.
"This is in the interests of Safety to motorists and also residents situated off the A38. Please find alternate routes we are working with Highways England to establish diversion routes so please be patient."
According to the Government Flood warning website, there is a high chance of flooding at the River Trent in Burton between 12am and 10am.
The warning urges people to call 999 if in immediate danger.
It says: "River levels have risen and are forecast to continue rising at the Drakelow river gauge as a result of heavy and persistent rainfall due to Storm Dennis.
"Consequently the flooding of property, roads and farmland is possible overnight between 12:00 AM and 10:00AM tomorrow, 18/02/20.
"We are closely monitoring the situation. Our incident response staff are actively checking river levels, the weather forecast and liaising with the emergency services.
"Please have a bag ready with vital items like medicines and insurance documents and call 999 if in immediate danger."