The ministry blamed the Israeli Air Force for pushing the Russian aircraft into the line of fire of Syrian missiles, saying it is not possible that Israel did not see the Russian plane as it was preparing to land.
The ministry said early on Tuesday that one if its military aircraft with 14 people on board disappeared from radar screens over Syria at the same time that Israeli and French forces were mounting aerial attacks on targets in Syria.
A U.S. official had said Washington believed the aircraft, which is an Il-20 turbo-prop plane used for electronic reconnaissance, was inadvertently shot down by anti-aircraft artillery operated by Moscow's ally, the Syrian regime.
Around the time the plane disappeared, the Syrian coastal city of Latakia, near a Russian airbase to which the Il-20 was returning, came under attack from "enemy missiles", and missile defense batteries responded, Syrian regime media reported.
The defense ministry in Moscow said the aircraft was returning to the Russian-run Hmeymim airbase in Latakia province when, at about 11:00 p.m. Moscow time (20:00 GMT) on Monday, it disappeared from radar screens.
The plane was over the Mediterranean Sea about 35 km (20 miles) from the Syrian coastline, Russia's TASS news agency quoted the ministry as saying in a statement.
"The trace of the Il-20 on flight control radars disappeared during an attack by four Israeli F-16 jets on Syrian facilities in Latakia province," the statement was quoted as saying.
"At the same time Russian air control radar systems detected rocket launches from the French frigate Auvergne which was located in that region."
The fate of the 14 people on board the missing plane is unknown, and a rescue operation has been organized out of the Hmeymim base, the ministry said.
Russia's military operation in Syria, which began in late 2015, has turned the tide of the conflict in favor of Moscow's ally, Syria's Bashar al-Assad, in his fight against opposition groups.
But it has come at a cost to Russia.
In December 2016, a Russian plane carrying dozens of Red Army choir singers, dancers and musicians crashed into the Black Sea on the way to Syria, killing all 92 people on board.
In March this year, a Russian military transport plane crashed when coming in to land at the Hmeymim base, killing all 39 people on board.
