Witnesses said the missile hit near a mosque in the Khan Yunis refugee camp early on Saturday while Israeli armoured forces gathered on the camp's outskirts.
Khan Yunis' hospital director said that a man of about 60 was killed by the missile and three other civilians were wounded in the strike.
The Israeli army offered no immediate comment.
The latest death brought to 4337 the number of people killed since the start of the Palestinian intifada four years ago. It includes 3318 Palestinians and 948 Israelis.