The voyage of the 33-foot (10-meter) catamaran comes nearly four months after Israeli commandos stopped a flotilla of Gaza-bound ships, clashing with passengers and killing nine pro-Palestinian activists.
Organizer Miri Weingarten says the Irene, which sailed from Cyprus on Sunday with 10 activists, should approach Gaza waters late on Monday.
The activists are trying to draw attention to Israel's blockade of Gaza. They say they will not resist if they are stopped.
The Israeli army declined to comment. Israeli Foreign Ministry spokesman Andy David has called the voyage "a politically motivated provocation."