Israel's military confirmed an Iranian missile struck the southern town of Dimona, home to a nuclear facility, leaving around 30 people wounded.
AFPTV footage showed a large crater and surrounding buildings with damaged facades and blown-out windows.
The Israeli army said there was a direct missile hit on a building, despite air defence interceptors being fired.
Magen David Adom first responders treated 33 people, including a 10-year-old boy in serious condition.
Iranian state TV said the attack was a response to an earlier strike on its own nuclear site at Natanz.