The plane, MH17, was flying from Amsterdam to Kuala Lumpur with 280 passengers and 15 crew, reports said.
Reports said that it crashed in a conflicted area near Donetsk and it would be complicated to get to the crash.
MAS sources said the plane did not enter the Russian airspace.
Sources said the plane was "shot down" while it was cruising at an altitude of 30,000ft.
Ukraine Interior Ministry said 295 people are feared dead in the crash.
The plane could have been brought down by ground-to-air missile, sources said.
MAS tweeted that "MAS has lost contact with MH17 from Amsterdam. The last known position was over Ukraine airspace."