US-Bangla's flight BS211 - carrying 67 passengers and four crew, 71 people in total - veered off the runway while landing about 2.20pm local time on Monday afternoon.
Officials said preliminary estimates indicate 49 people died and 22 others were injured in the crash.
An airport official, who spoke on condition of anonymity because of airport policy, said the plane appeared to have caught fire just before it landed and skidded to a stop in a field beside the runway. Flights to Kathmandu's Tribhuvan International Airport (TIA) are now holding or are being diverted.
The hill-ringed airport, based about six kilometres from the centre city, is the sole worldwide airport for the country and is located in the Kathmandu valley.
Manoj Nepune, the Kathmandu Police spokesperson confirmed over the phone that 14 people among the dead were of Nepalese nationality.
Another witness, Sushil Chandhury said the plane was "approaching from the opposite direction" to which aircrafts usually land.
The airline's chief executive officer Asif Imran said until the flight recorder or black box was recovered it would be impossible to "tell you about the actual reason of the accident".
The plane burst into flames after attempting to land at Kathmandu airport. The conversation between the air traffic controllers and the pilot, which was made public, suggested the pilot ignored instructions from the ground.
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Nepal's Prime Minister KP Sharma Oli and other politicos rushed to the spot and conveyed their condolence.
Nepal has been hit by air crashes in recent years, highlighting poor safety in the Himalayan country.
The two pilots and two cabin crew were Bangladeshi nationals, airline spokesman Kamrul Islam said in Dhaka.
Depending on the direction of approach, pilots have to fly over high terrain before making a steep descent towards the airport, Ascenzo said.
Those aboard included 33 Nepali passengers, with 32 from Bangladesh, one from China and one from the Maldives.
In March 2015, a Turkish Airlines flight crash-landed at Nepal's only global airport with no casualties.
Most accidents have been attributed to bad weather, inexperienced pilots and inadequate maintenance.
US-Bangla Airlines is a private airline operating since 2014 from Bangladesh's domestic airports.
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