The US said the strike was directed at "a known al-Qaeda terrorist", but did not say who.
A man in Kismayu, who said the house that was hit belonged to him, told Reuters news agency that his daughter was among the wounded.
"We do not know whether the missiles were fired by the American AC-130 plane which is still flying over the city. All we know is they dropped from the sky," Mohamed Nurie Salad said.
A local Somali politician, who asked not to be named, said: "The town is very tense. People have started fleeing because they fear there might be more attacks."
He said Sheikh Hassan Turki, a local leader, and other leaders of an armed group from Mogadishu, the capital, were meeting.
"This attack was against a known al-Qaeda terrorist," Bryan Whitman, a Pentagon spokesman said in Washington.
"As we have repeatedly said, we will continue to pursue terrorist activities and their operations wherever we may find them," he said.
He declined to provide details of the operation.
In January 2007, the US attacked southern Somalia in what was Washington’s first overt military action in the country since pulling out of a UN-backed peacekeeping mission in 1994.
That attack targeted members of the Islamic Courts fleeing from Ethiopian backing weak Somali forces during a two-week war to rout the movement.
In June 2007, a US navy destroyer shelled targets in mountainous and remote areas in northeastern Somalia where anti-government fighters were believed to have bases.
The US accuses Somali's anti-government fighters of supporting al-Qaeda members it believes was responsible for planning and executing the 1998 US embassy bombings in Kenya and Tanzania.