The Emirates flight EK9788, operating as Aerotranscargo, was arriving from Dubai at about 03:50 local time (19:50 GMT) when it hit a vehicle on the north runway.
Two airport ground staff fell into the sea, a statement from the Civil Aviation department says. They were rescued but later died in hospital, according to local media including public broadcaster RTHK which cited police.
The Airport Authority is set to host a press conference at 10:00 local time (02:00 GMT).
Two people in a ground staff vehicle that fell into the sea after a collision with the plane have died, local media have reported
The plane, a Boeing 747-481 (BDSF), was originally a passenger aircraft that was converted into a freighter.
It's more than 30 years old, having taken its first flight in 1993, according to aircraft tracking site Airfleets.
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On Monday, it was being operated as Emirates SkyCargo Flight 9788. It took off from Dubai on Sunday and arrived at Hong Kong International Airport around 03:50 local time (19:50 GMT).
Air ACT has another Boeing 747 in its fleet, according to flight tracking platform Flightradar24.
The Emirates flight EK9788, a Boeing 747-481 owned by Turkish cargo airline Air ACT, was arriving from Dubai at about 03:50 local time (19:50 GMT)
Four crew members onboard the plane survived Airport authorities are due to give a press conference at 10:00 local time (02:00 GMT)
This would be the second ever deadly incident at the current Hong Kong International Airport since it moved from Kai Tak to Chek Lap Kok in July 1998.
In August 1999, a China Airlines passenger flight crash landed hard during a typhoon, killing three people.
The north runway is still a relatively new entry to the Hong Kong airport's setup. It is now closed, while the airport sustains its operations with its centre and south runways, according to the airport authority.