"What's important is to avoid the partition of Syria and above all the religious struggle between the Shia, supported by Iran and in this case Russia, and the Sunni, supported by the Gulf states," Hollande said in an interview to be broadcast on Franco-German TV channel Arte on Sunday evening.
"You can clearly see the result," he continued. "It would be a war not just on a Syrian scale but across the whole region."
The US and other Western powers have accused Russia of bombing other Syrian opposition groups with the aim of propping up President Bashar al-Assad's embattled regime.
"In fact the strikes carried out by Russia have not primarily targeted Daesh [a pejorative acronym of IS]," Hollande said. "I reminded Vladimir Putin of that on Friday."
The Russian president is not an ally of the West "at the moment", he said, calling on him to become a "partner in the search for a political solution" and in "hitting Daesh".
Moscow has pledged to step up its air strikes, claiming that they are causing "panic" in IS's ranks.
On Saturday night its planes hit Raqa, regarded as IS's capital in Syria but Syrian sources say they have mostly hit the al-Qaeda-linked Al-Nusra Front and its Islamist allies, which have been the most effective in fighting Assad's forces this year.
Failure to solve the Syrian conflict will have consequences in the rest of the region and in Europe, according to Hollande, "because terrorism ... is prepared in the Syrian and Iraqi desert and then comes to strike us in our own country".