The media ethics inquiry is expected to focus on his relationship with figures in Rupert Murdoch's media empire.
Mr Cameron is a friend of ex-News International boss Rebekah Brooks and hired ex-News of the World editor Andy Coulson as his communications chief.
The inquiry is also likely to ask him about Culture Secretary Jeremy Hunt's handling of News Corp's BSkyB bid.
News Corp unveiled its bid for the satellite broadcaster in June 2010 but abandoned it in July 2011 amid outrage over the phone-hacking scandal at its now defunct News of the World (NoW) newspaper.
Politicians and media
The hacking scandal prompted Mr Cameron to launch Lord Justice Leveson's inquiry the same month.
His appearance before the inquiry at London's Royal Courts of Justice comes as it examines the relationship between politicians and the media.
It previously heard that Mr Hunt sent a memo to Mr Cameron voicing support for News Corp's bid for BSkyB before he was put in charge of overseeing it at the end of 2010.
Labour accuse Mr Hunt of being too close to News Corp before and during the BSkyB takeover process, in which he was given a "quasi-judicial" role.
But the prime minister has backed Mr Hunt amid calls for him to resign.