Iaquinta was a member of the Italian squad that won the 2006 FIFA World Cup under manager Marcello Lippi. His first international goal came in his nation's opening match of the tournament, on 12 June: Iaquinta scored Italy's second goal in the 2–0 victory against Ghana. He played in 5 out of 7 of Italy's matches, including the victorious semi-final against hosts Germany and final against France on 9 July, in which he came on after 61 minutes for Simone Perrotta. Iaquinta missed out on Roberto Donadoni's Italy squad for Euro 2008 due to injury. He later took part at the 2009 FIFA Confederations Cup, and he also played for Italy in the 2010 FIFA World Cup, in which he scored a penalty in a 1–1 draw against New Zealand in the second group match. His 40th and final international appearance came in the last group game on 24 June, in which Italy were defeated 3–2 by Slovakia and eliminated from the tournament. In total he scored six goals for Italy.