The comments by Russian Foreign Minister Sergei Lavrov came days ahead of scheduled Moscow talks between Russian President Vladimir Putin and a Syrian delegation.
"Possibly... This is not so much an operation against Islamic State as the preparation for an operation to change the regime surreptitiously under the cover of this anti-terrorist operation," Lavrov told a forum of politics experts in Moscow, quoted by TASS news agency.
He accused the US of having "perverted logic" over Assad, saying Washington blamed the Syrian leader's regime for the flood of militants arriving in the region.
Moscow has been a staunch ally of Assad's regime throughout Syria's civil war and has repeatedly thwarted UN action against him.
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Lavrov claimed that his US counterpart John Kerry told him that Washington did not get a mandate for the anti-IS operation from the US Security Council because this would require "defining the status of Assad's regime somehow."
"Syria is a sovereign country, a member of the UN. This is not right," Lavrov said.
The Russian foreign ministry said that Lavrov and Kerry held telephone talks yesterday in which they discussed the need for "renewing as soon as possible... The search for political and diplomatic ways to overcome the Syrian crisis and unite the efforts of the global community to fight terrorism on a stable basis of international law."
A Syrian delegation headed by Foreign Minister Walid Muallem is to meet Putin in Moscow on Wednesday to discuss a possible relaunch of peace talks with the opposition.