According to authorities, the crash occurred just before 5:00pm Saturday near 238 West Mount Laffee Road in New Castle Township.
Police say Amanda Smith, 28, of Branchdale was traveling on West Mount Laffee Road when she crossed the yellow line into the path of Desirae Davis, 32, of Shenandoah.
Smith was pronounced dead at the scene by Schuylkill County Deputy Coroner Mike Pothering.
Davis, and three children in the vehicle suffered injuries and were flown to an area hospital.
The crash is still under investigation.