Malaysia Airlines said it had lost contact with Flight MH17 from Amsterdam. The last known position was over Ukraine, it said in a tweet.
An aviation source in Moscow told Reuters the plane had been found burning on the ground in east Ukraine.
It had failed to enter Russian airspace, the source said.
Anton Herashchenko, an adviser to Ukraine’s interior minister, was quoted by the Associated Press as saying the plane had been hit by a missile at an altitude of 10,000m (33,000ft).
A number of military planes have been shot down by missiles in recent weeks over eastern Ukraine, where pro-Russian separatist rebels have been fighting government forces.
The UK Foreign Office said it was aware of the reports of the crash and was “urgently working to establish what has happened”.
This is the second major tragedy suffered by the airline in four months.
Malaysia Airlines Flight 370 from Kuala Lumpur to Beijing lost contact with air traffic control on March 8, 2014 less than an hour after takeoff.
The aircraft, a Boeing 777-200ER, was carrying 12 Malaysian crew members and 227 passengers from 14 nations.