Three men and a woman are trapped and four people have been taken to hospital after three explosions at a wood treatment works near Macclesfield.
A four-storey building collapsed at Wood Flour Mills in Tunstall Road, Bosley, at 09:10 BST, with large fires breaking out, the fire service said.
The fire service said it was a "scene of devastation". A search team is due to go into the site at first light.
Cheshire East Council said the blast has left 50 workers without jobs.
'Unsafe and hazardous'
Cheshire Police said 35 people on the premises were assessed at the scene with four people treated for breathing difficulties and another four people taken to hospitals in Birmingham, Merseyside and Stoke.
West Midlands Ambulance Service said: "A 29-year-old woman has sustained serious burns and blast injuries to her head, face, arms and chest."
She was taken by air ambulance to Queen Elizabeth Hospital Birmingham.
Cheshire Police's Assistant Chief Constable Guy Hindle said: "Four people remain unaccounted for and urban search and rescue teams are assessing the scene to see whether it is safe to go into the property to locate them.
"We are working with the four families."
Earlier, firefighters said they could not rule out further explosions.
Steve Barnes, from Cheshire Fire and Rescue Service, said: "When we arrived it was a scene of devastation. The surrounding area is unsafe and hazardous to firefighters."
He said the crews were trying to make the area safe to be in a position to carry out any potential rescue.
Chief fire officer Paul Hancock said: "We are still dealing with four unaccounted people. We believe they are somewhere in the building.
"We will endeavour to deal with that issue in a few hours' time once we get the incident under full control."
A search team is planning to go into the site at first light on Saturday, but there are still pockets of the building on fire.
The building contains heating oil, kerosene, acetylene and asbestos. There is also a silo containing highly flammable wood flour used for making wood laminate flooring.
'Worried for mates'
North West Ambulance Service (NWAS) sent six ambulances and two rapid response vehicles. An air ambulance was also at the scene.
An NWAS spokesperson said: "Two patients have been taken to Royal Stoke University Hospital and one patient has been taken to Whiston Hospital in Merseyside."
Emergency services said it was too early to ascertain what had caused the blaze.
Shift worker Patrick Jones, who clocked off his shift just over three hours before the blast, said: "I am still worried about my mates. There are four of them that are still missing."
He said he was not able to get through the cordon.
Police said smoke was drifting north east, with residents 15 miles away in Wildboarclough advised to close doors and windows.
More than 40 pupils at Bosley St Mary's C of E Primary School, which is about a mile from the explosion site, were kept inside the school building.
Raj Barard, headteacher, said: "We heard and we felt the explosion just after 09:00 BST. Police told us to keep the children indoors.
"It felt like an earthquake. We had our leavers service in the school instead of at the church over the road."
At the scene
BBC Radio Manchester reporter Jonathan Ali
Six hours later, the smoke plume is still hanging over this factory.
At around 14:40 there was the brief sound of popping noises as things continued to explode.
This was a four-storey factory which, in the words of the fire service, has now collapsed to one storey.
Basically it has collapsed in on itself.
Sarah Nixon, from Bosley Cloud, said: "I live less than half a mile from the wood flour mill and the explosion sounded as if a car had just crashed into the house with a very deep bang.
"The explosion shook the whole house rattling windows and doors, just like an earthquake.
"The black and grey smoke plummeted up along with flames and has engulfed the valley below."
Electricity North West said power was cut to 165 homes in Bosley to "allow firefighters to carry out their work safely". Power has since returned to the majority of homes.
Angela Shuker, who lives one farm along from the wood treatment works, said: "Our doors in the house just banged. We could see the flames rising not far from us down the road from the mill."
Charli Alston, 18, was walking her dog when she witnessed the explosion.
She said: "I was walking down my drive and there was just a huge bang. It sounded like a thunder cloud, we didn't know what it was.
"We looked over and there were massive plumes of flames. Almost as high as the hill next to it."
A blaze broke out at the wood flour mill in 2012.