Merseyside Fire and Rescue Service (MFRS) said it was called to a semi-detached property in Stone Square at 3.38am on Tuesday and arrived seven minutes later.
Chief fire officer Nick Searle confirmed the four deaths and said another person had been taken to hospital with burns after the “intense fire which spread very rapidly”.
Six engines were on scene at the height of the fire and eight firefighters entered the house to search for people and fight the blaze, said a spokesperson.
On Tuesday evening the fire service said: “Merseyside Fire & Rescue Service attended a house fire in Bootle on Tuesday, 22 September, and can sadly confirm that a woman and three children have tragically lost their lives in the fire.”
A neighbour said: “I heard shouting in the early hours but I just thought someone was having an argument, then I came downstairs and saw all the fire engines.”
The blaze was put out and the street remained cordoned off this morning as fire officers knocked at neighbouring properties.
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Kevin Longshaw, MFRS area manager, said: “This is a devastating incident, and our thoughts are very much with the family and friends of those who have lost their lives and been injured.
“We will work closely with relevant colleagues to ascertain the cause of the fire, but in the immediate term, we again extend our sincere condolences to those affected by this tragic incident.”
MFRS added: “A casualty outside the house on arrival of fire crews was taken into the care of North West Ambulance Service and taken to hospital suffering from burns.
“During the course of their search, firefighters discovered four casualties in an upstairs bedroom, showing no signs of life.
“Two members of North West Ambulance’s Hazardous Area Response Team were committed into the incident and tragically confirmed that all four had lost their lives.”
It said MFRS and Merseyside Police are now undertaking a joint investigation to establish the cause of the blaze.
Merseyside Police are investigating the circumstances.
