In June 2006, Boussoufa signed a 4-year contract with R.S.C. Anderlecht after a €3.5 million transfer. In his first season he was a regular in the title-clinching squad. He became a key player for the team that finished second in both the 2007–2008 and the 2008–2009 seasons.
Boussoufa was named Belgian Football player of the Year for a second time after the 2008–2009 season in which Anderlecht barely missed out on the title, losing the Championship play-off against Standard de Liège.
The next year, he managed 14 goals and 20 assists which made him the most valuable player in Anderlecht"s championship-winning squad. He was named Belgian Football player of the Year for a second consecutive time and the third time overall.
After the season he renewed his contract with a significant raise, making him the best paid football player in Belgium. On 7 March 2011, Russian side Football Club Terek Grozny announced his signing, but his transfer fell through three days later.
According to Terek"s VP Khaidar Alkhanov, Boussoufa requested unacceptable conditions in his personal contract, even though Anderlecht had agreed to sell him.
In the late evening of 10 March, it was announced that the transfer to Terek Grozny had collapsed and that Boussoufa had signed for another Russian team, Anzhi Makhachkala. On 16 August 2013 he signed a 3-year contract with Football Club Lokomotiv Moscow. On 1 February 2016 he returned to K.A.A. Gent on loan from Lokomotiv Moscow.
Boussoufa has a Dutch passport and as such would have been eligible to play for the Dutch national team if selected, but chose Morocco and played his first match for the Moroccan national team against the United States of America on 23 May 2006.