The drive - which will see the online travel company swell its UK ranks to more than 100 - comes as it gears up to launch a pan-European cross-media campaign worth about £4 million in the UK.
The company needs to fill key positions including UK web site manager, a role currently being handled by the manager of the German site, and alliances account manager, which covers all online partnerships with companies including MSN, Google, Ask Jeeves UK, Tiscali and BTLookSmart.
"This drive is focused on recruiting for senior positions in the London headquarters, but opportunities may arise in our European offices over time," said Lorraine Twohill, head of market development at Opodo.
Twohill added that the expansion of the UK operation was being undertaken because of its current performance and future predicted growth.
The cross-media campaign, which kicks off at the end of September, will run in the UK, France and Germany. It will see Opodo make its first foray into TV advertising, using singer Iggy Pop's track Lust for Life.
Online ad activity will include executions with long-term partners such as Google and Ask Jeeves UK (www.ask.co.uk). Ads will also run across ISPs and travel web sites, including Virgin, Freeserve and Associated New Media's This Is Travel.