The Russian military said an An-26, with 33 passengers and six crew members onboard, crashed just 500 meters (1,600 feet) from the runway. The military blamed the crash on a technical error and insisted that the plane was not shot down.
All of the people on board were Russian servicemen, the ministry said.
Russia, a key ally of Syrian President Bashar Assad, leases the Hemeimeem military base in Syria, near the Mediterranean coast.
The base is far from the front lines of the conflict, but came under shelling in December. The Russian military insisted the cargo plane did not come under fire, while saying it would conduct a full investigation.
President Vladimir Putin offered his condolences to the families of those killed in the crash after receiving a briefing by Defense Minister Sergei Shoigu, the Kremlin said.
Prime Minister Dmitry Medvedev in a statement on the government's website said he was "deeply shaken" by the crash, which had caused "an irreparable loss."
The Interfax news agency quoted a spokeswoman for Russia's Investigative Committee, which handles high-profile cases, as saying Russian investigators have been dispatched to Syria to look into the crash.
It was the second Russian military plane to crash in Syria this year, after a Su-25 ground attack jet was struck by a portable air defense missile over the northern Idlib province last month.
The Antonov An-26 is a twin-engine transport plane designed in the late 1960s in the Soviet Union. Large numbers have remained in service in Russia and many other countries around the world.
An An-26 belonging to a military flight school crash-landed and caught fire southeast of Moscow in May, killing one crewmember.
The RIA Novosti news agency on Tuesday quoted Col. Gen. Nikolai Antoshkin, former deputy commander of the Russian Air Force, as calling the An-26 a "reliable machine" even though it has been out of production since 1986.
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