The crash, involving two vehicles, happened at about 20:15 BST on the B1102 Freckenham Road in Worlington, near Barton Mills.
Police said: "It is believed that two vehicles were in collision, one vehicle left the road, ended up in the front garden of a home and caught fire."
An investigation has started and any witnesses are asked to call the police.
Police said the road would be closed while a "serious collision investigation takes place".
Officers from Suffolk Police, Suffolk Fire and Rescue Service and East of England Ambulance service attended the scene.
Four people have been killed in a road crash in Suffolk in which one vehicle ended up in a garden and caught fire.