Squillaci began his football career playing for hometown club FC Seynois in the commune of La Seyne-sur-Mer. In 1996, he joined Toulon and made his professional debut in the 1997–98 season, while the club was playing in Ligue 2. After a year with Toulon, Squillaci joined Monaco. He spent two seasons on the club's reserve team before joining AC Ajaccio on loan for two years. Squillaci returned to Monaco in 2002 and contributed to the team that won the Coupe de la Ligue in 2003. He also featured in European competition for the first time in his career and, in the 2003–04 season, played on the Monaco team that reached the 2004 UEFA Champions League Final. In the same season, Squillaci was named to the National Union of Professional Footballers (UNFP) Ligue 1 Team of the Year. In 2006, Squillaci signed a long-term contract with league rivals Olympique Lyonnais and won two consecutive league titles, as well as the Coupe de France in 2008 before departing for Spain in 2008 to join Sevilla. With Sevilla, he appeared in over 65 matches and won the Copa del Rey in his final season with the club. In 2010, Squillaci signed a three-year contract with English club Arsenal where he also reached 2011's Football League Cup final.