The crash involved just one vehicle in Yew Tree Drive (A6119) shortly before midnight, between the junctions with A677 Preston New Road and Whinney Lane.
Police said a man had been pronounced dead at the scene and an investigation is underway to establish what happened.
A spokesman for Lancashire Police said: "We were called at shortly before midnight on Tuesday to reports of a single vehicle collision on Yew Tree Drive at Blackburn.
"Police attended and a man was sadly pronounced dead at the scene.
"Enquiries are ongoing and the road remains closed at this time."
North West Ambulance Service said there were no other casualties.
A spokesman for North West Ambulance Service said: "We were called there at 11.47pm and attended with a rapid response vehicle, two ambulances, advanced paramedic and tactical commander.
"We treated one casualty."
Yew Tree Drive remains closed in both directions this morning, leading to traffic delays along Preston New Road towards Preston.
There are reports of heavy traffic in the area, with motorists being diverted along Barker Lane and through the village of Mellor, before joining Preston New Road at the junction with Mire Ash Brow.
Stagecoach has also diverted its 59 service between Preston and Blackburn and this means it will not serve Preston New Road/New Hall Lane.
The diversion will be via Preston Old Road (152 route) onto Buncer Lane and returning to route at Billenge Lane. The route will be the same on return.