The move follows a process that involved Confused.com meeting with agencies including Leo Burnett, Rainey Kelly Campbell Roalfe/Y&R and Adam & Eve.
Confused.com began contacting agencies in September last year but Mike Hoban, its marketing director, denied at the time that he would make an agency appointment.
In recent years, the bulk of the price-comparison site's advertising activity has been created in-house.
The company hired Beattie McGuinness Bungay to handle its business in October 2009, but parted with the agency just nine months later.
After the split with BMB, Confused.com launched a new campaign featuring an animated mascot called Cara.
Publicis will now be responsible for building on this campaign. Confused.com, which currently spends £28 million on advertising, according to Nielsen, is raising its marketing spend to £50 million in 2012. PHD handles its media planning and buying.
Hoban said: "The Cara campaign has proved to be a great success and now we look forward to Publicis helping us take Confused.com's advertising to the next level."
Publicis' appointment follows news last week that Confused.com's rival, Gocompare.com, is preparing to kick off its own search for an advertising agency.