The Katusha rider had broken away alongside Stijn Vandenburgh of Omega Pharma-Quick Step, and the two remained over fifty seconds clear of the peloton entering the final kilometre.
Paolini moved first and kept Vandenbergh at bay to take the victory in the first Belgian classic of the season.
Sven Vandousselaere of Topsport Vlaanderen-Baloise won the sprint for third place.
"I'm absolutely happy about this win," said Italian rider Paolini.
"It's a very important victory both for me, for Katusha and for Russia, since today I know is the Russian Men's Day: I'm very pleased to give them another reason to celebrate.
"It was a special triumph for me in a very prestigious competition, one of the most beautiful Belgian classic race. I felt in a great condition despite the cold weather, and in the end I managed to win thanks also to my bigger experience.
"I have to thank the whole team, they worked great: in the morning we decided the strategy, and everything went as we planned."