The victory keeps Roma in the title race after Max Tonetto and Christian Panucci's goals sandwiched an effort from Empoli midfielder Sebastian Giovinco.
"I have been doing this job for quite a few years now and have never found a single easy game," said Roma coach Luciano Spalletti.
"Empoli deserve to be higher up the table. The fact we were able to win this match even when a man down means we had the best possible reaction. Losing the derby does take away something in terms of enthusiasm.
"When we went down to 10 men our crowd gave us an exceptional push. If they react that way then they must know that they give us a great hand. If they act like they did at the start of the match, then that creates tension."