The Airbus A320 was flying at 37,000 feet when it disappeared shortly after entering Egyptian airspace at 2:45 am local time, an airline official said.
Thae flight number MS804 lost contact with radar above the Mediterranean Sea about 280 km from the Egyptian seacoast.
The airliner said in a statement that there were 56 passengers in addition to 10 cabin crew members on board.
Apart from 30 Egyptians, the plane was carrying 15 French passengers, two Iraqis and one each from Britain, Belgium, Kuwait, Saudi Arabia, Sudan, Chad, Portugal, Algeria and Canada.
The Egyptian military has deployed search aircraft and naval vessels to locate the plane, in cooperation with Greece.
An EgyptAir official said the search was focused on an area of sea north of the Egyptian coast, without providing a precise location.
In March, another EgyptAir flight from Alexandria to Cairo was hijacked and forced to divert to Cyprus, where the hijacker demanded to see his former wife.
He had claimed he was wearing an explosive vest, which turned out to be fake, and surrendered within hours after freeing the passengers and crew.
The group said it had smuggled a bomb concealed in a soda can on board the plane at Sharm El-Sheikh airport.
The airliner has hosted the passengers' families near to Cairo Airport and has provided doctors, translators and all the necessary services to the passengers' family members during their stay at Cairo Airport.
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