Emergency services rushed to the home in Gum Court, Bushland Beach about 5.30am today.
Authorities were forced to smash the top floor window to enter the flaming building and pull out the girls, aged two and 13.
Police said they were taken to Townsville University Hospital in a life-threatening condition.
Two other children are also in hospital in a stable condition.
Two police officers were treated for smoke inhalation and taken to hospital as a precaution.
Investigations are ongoing.
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