Video filmed by a Tass Agency reporter showed one group advancing on the other and at one point surrounding one man in a white t-shirt who stumbled and held on to a railing as men hit him.
The fleeing crowd ran onto a square before a police officer ran toward the opposite group and opened a can of pepper spray directly onto the faces of the violent Euro fans.
The clash late on Tuesday came hours after a small group of Russian and English fans scuffled in the northern city as thousands of supporters arrived in the area for the next round of matches.
Lille is seen as a potential trouble-spot as Russia is set to play Slovakia on Wednesday and England fans are also congregating there ahead of their match against Wales in nearby Lens on Thursday.
Violence between rival fans has marred the start of the 24-nation championship and given an extra headache to police and security forces already pre-occupied with guarding against any Islamist militant threat.
The regional police chief in Lille has said the sale of alcohol would be banned from Tuesday evening until Friday morning and bars in the center would be closed from midnight Wednesday until Thursday evening.
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