The fire broke out just after 3 a.m. in a house on North 12th Street in New Hyde Park.
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Officials say the house was fully engulfed in flames by the time firefighters arrived, and the fire was so intense it had blown out the doors and windows of the home.
Another grandchild, a 10-year-old boy, escaped the fire by jumping out of a second story window and landing on top of a car.
The boy ran across the street to get help from a neighbor's house.
"There were three people that were in the house, all did get transported to area hospitals," said New Hyde Park Fire Chief Brian Sherwood. "One child did come out the front window on his own. There was a car underneath that broke his fall, but he did get transported as well."
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The grandfather, who was home at the time of the fire, survived. The parents of the children were out of town.
Several neighboring fire departments were called in to help. It took about 90 minutes to get the fire under control.
The Nassau County Fire Marshal is investigating the cause of the blaze. Arson/Bomb Squad detectives said the fire does not appear to be suspicious.
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