The 33 year-old man was transported to the Royal Brisbane and Women's Hospital after the fire near Logan early on Thursday morning and died shortly after 10pm.
A 31-year-old woman believed to be known to the man but not living at the home was also killed in the blaze, and an autopsy will confirm her identity.
"We believe the person who does not reside at that residence somehow gained entry and then once in there was able to throw petrol around," Superintendent Mark White said on Thursday.
A domestic violence link between the man and a former partner is forming part of the investigation.
Paramedics arrived at around 3am to find five people outside the home as firefighters tried to extinguish the blaze.
"We have arrived to find that a house was pretty well engulfed in flames," Ambulance Operations Supervisor Simon McInnes said in a statement on Thursday.
Three children - aged two, three and five - were not injured.
Paramedics took a second woman, aged 30, to hospital with suspected airway burns.
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