Suffolk County police say surrounding houses also were damaged. The blast happened just before noon Tuesday in Brentwood.
Video footage from a News12 Long Island helicopter showed firefighters and police officers digging through a huge pile of rubble.
At least one person was pulled out on a stretcher and airlifted to a hospital.
Neighbors many blocks away reported feeling their own homes shake.
WCBS Radio says a neighbor's arms and hands were bloodied from digging through the rubble to look for victims.
National Grid spokeswoman Wendy Ladd says it appears natural gas was not used in that house or on the entire block.
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