The fatal collision happened outside Strabane, Co Tyrone on Melmount Road between Sion Mills to Victoria Bridge just before 11 am.
The PSNI said the collision involved a black Suzuki Vitara jeep and a blue Toyota Avensis happened.
The fatal victim was a passenger in one of the cars.
Two men, one in his 20s and one in his 40s and two women, one in her 20s and one in her 50s have been taken to hospital for treatment for their injuries
Police have described their conditions as serious.
Emergency teams, including four fire appliances and along crews of paramedics, rushed to the scene to render aid to the injured at the crash scene.
As a result of the crash, police erected diversions at Victoria Bridge as emergency crews worked at the scene.
Police have appealed to anyone who witnessed the collision or anyone who was travelling on the Melmount Road around the time of the crash to contact them at the Collision Investigation Unit at Steeple Police Station or Strabane Police Station on 0845 600 8000.