The company has shortlisted three London-based digital shops with a brief to revamp and rebuild www.E4.com, make it more interactive and expand its range of content.
James Tatam, the business manager at E4.com, said: "E4 is an innovative, irreverent brand and the relaunch of the website will bring the channel even closer to its young and engaged audience."
Profero currently handles online creative, strategy and media for Channel 4, E4, Film4 and More 4. It is not involved in the pitch.
The E4 site was abandoned in 2002, when it was integrated into channel4.com. It was resurrected this year and used as a platform for Big Brother applications and for hosting E4 programme information.
The pitch comes as ad revenues from Channel 4's digital TV division continue to grow. According to its 2006 annual report, Channel 4's new-media division more than doubled its turnover to £51 million year on year.