In 2004 he was selected by coach John Kirwan to represent Italy against England in the 2004 Six Nations Championship. Griffen had a successful tournament and was voted Italy's best player alongside Andrea Lo Cicero. He was replaced as first choice scrum-half by Alessandro Troncon for the 2005 Six Nations Championship, appearing as a replacement on two occasions. He remained a regular member of the Italy squad until 2007. The highlight of Griffen's career was his selection by Italy coach Pierre Berbizier for the 2007 Rugby World Cup, where he appeared in three games. Griffen was omitted from the national team for the 2008 Six Nations Championship, but was recalled after a 16-month absence by new Italy coach Nick Mallett for the 2009 Six Nations Championship, where he made four appearances.