The EU is demanding the "immediate" halt of Russian air strikes against moderate Syrian rebel groups, warning a lasting peace is impossible under Moscow-backed President Bashar al-Assad.
EU foreign policy chief Federica Mogherini on Monday called Russia's military intervention in Syria an unwelcome "game-changer" that jeopardised peace efforts and risked clashes with western aircraft targeting Islamic State jihadists.
"The recent Russian military attacks that go beyond Daesh [IS] and other UN-designated terrorist groups, as well as on the moderate opposition, are of deep concern and must cease immediately," the EU's 28 foreign ministers said in a statement on Monday (local time).
"This military escalation risks prolonging the conflict, undermining a political process, aggravating the humanitarian situation and increasing radicalisation," they said.
EU leaders meet on Thursday for a summit likely to be dominated by the Syrian conflict which has claimed some 250,000 lives and driven about 12 million people - half the population - to flee their homes.
Many of them have given up hope of an end to the war and have flooded into Europe seeking refuge, helping drive the worst migrant crisis since World War II.
Russian President Vladimir Putin said on Sunday Russia's military actions in Syria were meant to "stabilise the legitimate authorities and create conditions for finding a political compromise."
Russia, which insists its attacks on "terrorists" include IS targets, has important military facilities in Syria and has backed Assad and his father before him against all rivals for decades.
Meanwhile in Moscow, the defence ministry said its planes hit 53 targets in Syria over the past 24 hours as it steps up its bombing campaign.
Russian jets conducted strikes in the provinces of Hama, Homs, Latakia and Idlib and destroyed "terrorist" command posts, defensive positions, training camps and ammunition depots, the ministry said in a statement.
It said the bombing raids had severely disrupted supply chains for IS fighters.
EU foreign ministers for their part urged Russia to "focus its efforts on the common objective of achieving a political solution to the conflict."
They said this required "a peaceful and inclusive transition" but it was not clear if Assad would have any role in it, reflecting sharp divisions over his immediate future.
For the longer term, ministers agreed he had no place in Syria.
"There cannot be a lasting peace in Syria under the present leadership and until the legitimate grievances and aspirations of all components of the Syrian society are addressed," they said.