The plane, carrying 227 passengers and 12 crew members, lost communication two hours into the flight in Vietnam's airspace at 1.20am local time, China's official Xinhua News Agency reports.
The aircraft left Kuala Lumpur for Beijing 12: 11 am on Friday and had been expected to arrive China at 6:30 am but lost contact with traffic controllers over the South China Sea between Malaysia and Vietnam.
Passengers were from 14 countries, including 153 from China, 38 from Malaysia, seven Australians and four Americans.
Search & rescue have begun and families and next of kin of passengers and crew have been notified. (The last time a plane went missing like this, the plane, an Air France aircraft, was eventually found in the Atlantic Ocean, resulting in the deaths of 228 people. This was in 2009.