Damascus also accused Israel of carrying out the strike.
"Two F-15 planes of the Israeli army hit the airbase between 03:25 am and 03:53 am Moscow time with the help of eight missiles controlled remotely from Lebanese territory, without entering Syrian air space," the Russian defence ministry said.
Five of the missiles were destroyed by Syrian defence systems but the remaining three struck "the western part of the airbase" in Homs, the ministry's statement added.
At least 14 fighters, including Iranians, were killed in the strike on the T-4 airbase, according to the Syrian Observatory for Human Rights.
Russian and Iranian forces, as well as fighters from Hizballah, are reported to have a presence at the base.
No Russian specialists present in Syria were injured in the attack, Moscow's defence ministry said.
A military spokeswoman for Israel declined to comment on the strike. However, Israel has frequently struck Syrian military positions since the war broke out in 2012. Tel Aviv views Hizballah, an Iranian-backed regime ally, as its biggest threat and has grown alarmed over Tehran's growing clout in Syria.
Syrian state TV had previously charged the US with striking the military base, calling it a likely "act of aggression". But a Pentagon spokesman denied the charge, saying "at this time, the Department of Defence is not conducting air strikes in Syria".
France also denied any involvement in the strike.
US President Donald Trump had previously tweeted there was a "big price to pay" for the chemical weapons attack on Saturday in Eastern Ghouta that left 49 dead.
The Syrian regime denied any involvement in the chemical attack, and Moscow called the allegations "fabrications" and "fake news". However, the regime has repeatedly denied using chemical weapons despite a September 2017 UN report that found it responsible for using chemical weapons on more than two dozen occasions.
Last year, the US launched several dozen Tomahawk cruise missiles at a Syrian air base after a chemical attack in the northern Syrian town of Khan Sheikhoun killed dozens of people.
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