The Russian-made AN-24 was travelling from the town of Siem Reap, close to the famous ruins of Angkor, en route to the beach resort of Sihanoukville.
It vanished from radar screens five minutes before it was due to land, officials said.
Hun Sen said the government was offering a $5,000 reward to anyone who found the crash site or retrieved dead bodies.
"It is a big disaster for Cambodia"
"Even though only a small number of people died, it is a big disaster for Cambodia," he said in the capital, Phnom Penh, earlier on Tuesday.
"We must find the dead bodies and send them back to their families... We have little hope that those people are still alive, but we must try our best to help them."
The aircraft, operated by a small Cambodian airline called PMT Air, is thought to have crashed in a mountainous area about 50 kilometres from its destination.
Keo Sivorn, the Cambodian civil aviation safety chief, said bad weather could have caused the aircraft to crash but "nothing can be certain until we find the plane and analyse the black box".
|South Koreans made up a large portion of the |
1.7m visitors to Cambodia in 2006 [EPA]
"We just still don't know what happened to the plane. The pilot could have managed an emergency landing or could have hit the mountain," he added.
The 22 people on board included 13 South Koreans, three Czech nationals, a Russian pilot and five local crew members.
More than 1,000 police, soldiers and local conservation workers were scouring the area guided by vague eyewitness accounts from villagers.
Heavy rains also grounded five helicopters, hampering any progress in the rescue efforts.
Ly Thuch, deputy director of Cambodia's National Disaster Committee, said Cambodia has asked the US Embassy to help provide satellite images of the area to try and locate the crash site.
"We hope to find them soon. The [rescuers] will search deeper into the forest," he added.
PMT Air opened a route between Siem Reap, home to the 800-year-old Angkor Wat temple complex, and Sihanoukville in January, aviation officials said, in a bid to encourage more tourist traffic between the two cities.
The crash is the first major aircraft disaster to strike Cambodia in a decade.
In Cambodia's last major air accident in 1997, 64 people died when a Vietnam Airlines aircraft flying from Ho Chi Minh City crashed while trying to land at the Phnom Penh international airport during heavy monsoon rains.
Only a Thai boy and a Vietnamese boy survived the crash.