The strike, which Russian news agencies said was the first of its kind since November, was carried out by the frigate Admiral Essen and the submarine Krasnodar, and targeted terrorists and equipment in an area east of Palmyra.
The defence ministry said the hardware and forces struck had previously been deployed by ISIS in Raqqa.
"All targets were destroyed," it said in a statement.
Russia had warned the United States, Turkey and Israel before launching the missiles, the ministry said.
The last time Russia fired Kalibr cruise missiles from its ships at ISIS targets in Syria was in November last year, the RIA news agency said.
Separately, photographs published today by Turkish bloggers for their online Bosphorus Naval News project showed a Russian Syria-bound ship passing through the Bosphorus carrying a consignment of military trucks.
(Reporting by Maria Kiselyova/Dmitry Solovyov/Jack Stubbs; Editing by Andrew Osborn)
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